Wales Cancer Research Conference 2025 - Programme and abstracts

Wales Cancer Research Conference 2025

3 March 2025 International Convention Centre (ICC), Newport Programme and abstracts

FILMING AND PHOTOGRAPHY

We will be filming and taking photographs during the Wales Cancer Research Conference. All film/photos will be used for PR and marketing purposes promoting the Wales Cancer Research Centre and partners. If you would prefer not to be included in photographs, please let a member of our Hub team know before the end of the conference.

Byddwn ni’n ffilmio ac yn tynnu lluniau yn ystod Cynhadledd Ymchwil Canser Cymru. Bydd yr holl ffilmiau/lluniau’n cael eu defnyddio at ddibenion cysylltiadau

cyhoeddus a marchnata er mwyn hyrwyddo Canolfan Ymchwil Canser Cymru a phartneriaid. Os byddai’n well gennych chi beidio â chael eich cynnwys yn y lluniau, rhowch wybod i aelod o’n tîm cyn diwedd y gynhadledd.

Please do not share or reproduce abstract, poster or presentation content from this event; please treat data presented as confidential.

Peidiwch â rhannu nac atgynhyrchu cynnwys crynodeb, poster na chyflwyniad o'r digwyddiad hwn; dylech drin data a gyflwynir yn gyfrinachol.

Director’s welcome/Croeso gan y Cyfarwyddwr

Programme/Rhaglen

About the Wales Cancer Research Centre/ Ynglŷn â chanolfan Ymchwil Canser Cymru

Meet today’s sponsors

Conference Chair and keynote speakers

Patient and Public Involvement

Lightning talks: Precision and mechanistic oncology, Immuno-oncology and Radiotherapy

Lightning talks: Cancer clinical trials, Palliative and supportive oncology and Population health-based cancer prevention and early detection

Breakout session: Wales’ spinouts - new innovations from lab to clinic

Breakout session: Cancer prevention and early detection

Sponsor spotlight session

Breakout session: Mechanistic oncology

Breakout session: Clinical trials

Debate speakers

Professor Mererid Evans Director, Wales Cancer Research Centre

Dear delegates,

Following the success of our inaugural conference last year, I am delighted to welcome you to the Wales Cancer Research Conference 2025! At the Wales Cancer Research Centre (WCRC) we work in partnership to develop and support excellent cancer research across Wales Aligned with the all-Wales Cancer Research Strategy (CReSt), we're focused on growing the cancer research base in Wales for the benefit of our population and patients

Today will bring together clinical and non-clinical cancer researchers and stakeholders from across the country, at all career stages, from basic science, to translational work, to the clinic, to spinout companies and beyond We hope to showcase the impressive breadth of expertise across all areas of cancer research in Wales.

We welcome speakers from around the UK to share valuable insights into their work, to inspire and build partnerships with Welsh researchers We hope today will serve as a wonderful opportunity for collaboration and networking.

We were overwhelmed by the volume and quality of the abstracts submitted to the conference, and we encourage everyone to take time to attend the lightning talks, and view the posters on display This highlights the incredible amount of research being undertaken in Wales, and is a great reminder of the value of Welsh scientific contribution to cancer research as a whole

Today would not be possible without our funders, Health and Care Research Wales, our hosts at the International Conference Centre, and the generosity of our sponsors, to whom we’re very grateful.

Let the Wales Cancer Research Conference 2025 commence!

Yr Athro Mererid Evans

Cyfarwyddwr, Canolfan Ymchwil Canser Cymru

Annwylgynrychiolwyr,

Yn dilyn llwyddiant ein cynhadledd agoriadol y llynedd, mae’n bleser gennyf eich croesawu i Gynhadledd Ymchwil Canser Cymru 2025! Yng Nghanolfan Ymchwil Canser Cymru (WCRC) rydyn ni’n gweithio mewn partneriaeth i ddatblygu a chefnogi ymchwil canser rhagorol ledled Cymru. Yn unol â Strategaeth Ymchwil CanserCymruGyfan(CReSt),rydynni’ncanolbwyntioardyfusylfaenymchwilcanseryngNghymruerbuddein poblogaetha’ncleifion.

Bydd heddiw yn dod ag ymchwilwyr canser clinigol ac anghlinigol a rhanddeiliaid o bob rhan o’r wlad ynghyd, ar bob cam gyrfaol, o wyddoniaeth sylfaenol i waith trosiadol, i’r clinig, i gwmnïau deillio a thu hwnt. GobeithiwnarddangosehangdertrawiadolyrarbenigeddymmhobmaesymchwilcanseryngNghymru.

Rydyn ni’n croesawu cyflwynwyr o bob rhan o’r DU i rannu cipolwg gwerthfawr ar eu gwaith, i ysbrydoli a datblygu partneriaethau gydag ymchwilwyr Cymreig. Gobeithiwn y bydd heddiw yn gyfle gwych i gydweithio a rhwydweithio

Cawsom ein syfrdanu gan nifer ac ansawdd y crynodebau a gyflwynwyd i’r gynhadledd, ac rydyn ni’n annog pawb i gymryd amser i ddod i’r cyflwyniadau cyflym a gweld y posteri sy’n cael eu harddangos. Mae hyn yn amlygu’r swm anhygoel o ymchwil sy’n cael ei wneud yng Nghymru ac mae’n ffordd wych o’n hatgoffa o werth cyfraniadgwyddonolCymruatymchwilcanseryneigyfanrwydd.

Ni fyddai heddiw wedi bod yn bosibl heb ein harianwyr, Ymchwil Iechyd a Gofal Cymru, ein cynhalwyr yn y GanolfanGynadleddaRyngwladol,ahaelionieinnoddwyr,yrydynni’nddiolchgariawniddynnhw.

GadewchiGynhadleddYmchwilCanserCymru2025ddechrau!

Morning sessions 9:15-12:50

09:15 - Introduction: Prof Mererid Evans (Wales Cancer Research Ce

09:25 - Keynote: Prof Serena Nik-Zainal (University of Cambridge

Mutational signatures in cancer: from mechanism to medicine

10:05 - Patient and public involvement: Bryan Webber

A patient’s experience of being part of research

10:25 - Lightning talks: Oral abstract presentations

Dr Marcos Quintela (Mechanistic oncology)/Dr Marta Williams (Immuno-oncology)/

Dr Emma Higgins (Radiotherapy)

10:45 - Refreshment break and poster viewing

11:15 - Lightning talks: Oral abstract presentations

Dr Karam Aboud (Clinical trials)/Dr Ope Gbadegesin (Palliative and supportive oncology)/

Dr Tracy Knight (Population health-based cancer prevention and early diagnosis)

11:45 - Wales’ spinouts: new innovations from lab to clinic

Prof Simon Reed (BrokenString)

The evolution of BrokenString

Prof Dean Harris (CanSense)

CanSense Ltd: commercialisation journey for early detection of colorectal cancer

Prof Alan Parker (Accession Therapeutics)

From bench to bedside - taking a new virotherapy across the valley of death

11:45 - Cancer prevention and early detection

Prof Antonis Antoniou (University of Cambridge)

Personalising cancer risk prediction for prevention and early detection

Dr Stephanie Smits (Public Health Wales)

Cancer registry data in cancer research

Afternoon sessions 12:50-17:30

12:50 - Lunch break, networking and poster viewing

13:35 - Wales Cancer Industry Forum spotlight session

14:05 - Keynote: Prof Andrew Beggs (University of Birmingham)

Long reads and Liquid Biopsies: genomic medicine at the cutting edge

14:55 - Mechanistic oncology

Prof Awen Gallimore (Cardiff University)

Blood vessel modification to boost immune attack of cancer

Dr Eileen Parkes (University of Oxford)

Chromosomal instability and response to immunotherapy

14:55 - Clinical trials

Prof Krishna Narahari (Cardiff and Vale University Health Board)

Role of Lymph node excision in Prostate Cancer- The ELIPSE Study

Dr Anna Kirby (University of Cambridge)

Testing a 1-week simultaneous integrated boost in breast cancer radiotherapy: The FAST-Forward Boost Trial

16:00 - Refreshment break and poster viewing

16:30 - Debate: “Immunotherapy is a panacea for cancer”

Moderator: Dr Martin Rolles (NHS Wales)

Against: Prof Andy Godkin (Cardiff University)

For: Dr Ben O’Leary (Institute of Cancer Research)

17:10 - Poster and presentation awards

17:20 - Closing remarks: Prof Mererid Evans (Wales Cancer Research Centre)

17:30 - Networking reception and poster viewing

bore 9:15-12:50

09:15 - Cyflwyniad: Yr Athro Mererid Evans (Canolfan Ymchwil Canser Cymru)

09:25 - Prif Araith: Yr Athro Serena Nik-Zainal (Prifysgol Caergrawnt)

Arwyddion mwtanol mewn canser: o fecanwaith i feddyginiaeth

10:05 - Cynnwys Cleifion a'r Cyhoedd: Bryan Webber

Profiad y claf o fod yn rhan o ymchwil

10:25 - Cyflwyniadau cyflym: Cyflwyniadau crynodeb llafar

Dr Marcos Quintela (Oncoleg fecanistig)/Dr Marta Williams (Imiwno-oncoleg)/Dr Emma

Higgins (Radiotherapi)

10:45 - Egwyl lluniaeth a chyfle i edrych ar y posteri

11:15 - Cyflwyniadau cyflym: Cyflwyniadau crynodeb llafar

Dr Karam Aboud (treialon clinigol)/Dr Ope Gbadegesin (oncoleg liniarol a chefnogol)/

Dr Tracy Knight (Atal canser sy'n seiliedig ar iechyd y boblogaeth a diagnosis cynnar)

11:45 - Cwmnïau Deillio Cymru: datblygiadau arloesol newydd o'r labordy i'r clinig

Yr Athro Simon Reed (BrokenString)

Esblygiad BrokenString

Yr Athro Dean Harris (CanSense)

CanSense Ltd: Taith fasnacheiddio ar gyfer canfod canser y colon a’r rhefr yn gynnar

Yr Athro Alan Parker (Accession Therapeutics)

O’r fainc i’r gwely - cymryd firotherapi newydd ar draws dyffryn y meirw

11:45 - Atal a chanfod canser yn gynnar

Yr Athro Antonis Antoniou (Prifysgol Caergrawnt)

Personoli’r gwaith o ragfynegi risg canser ar gyfer atal a chanfod canser yn gynnar

Dr Stephanie Smits (Iechyd Cyhoeddus Cymru)

Data'r gofrestrfa canser mewn ymchwil canser

Sesiynau prynhawn 12:50-17:30

12:50 - Egwyl ginio, rhwydweithio a chyfle i edrych ar y posteri

13:35 - Sesiwn sylw ar Fforwm Diwydiant Canser Cymru

14:05 - Prif Araith: Yr Athro Andrew Beggs (Prifysgol Birmingham)

Darlleniadau hir a biopsïau hylif: meddygaeth genomig arloesol

14:55 - Oncoleg fecanistig

Yr Athro Awen Gallimore (Prifysgol Caerdydd)

Addasu pibellau gwaed i hybu ymosodiad imiwn ar ganser

Dr Eileen Parkes (Prifysgol Rhydychen)

Ansefydlogrwydd cromosomaidd ac ymateb i imiwnotherapi

14:55 - Treialon clinigol

Yr Athro Krishna Narahari (Bwrdd Iechyd Prifysgol Caerdydd a'r Fro)

Gofal sy'n seiliedig ar dystiolaeth: treial ELIPSE

Dr Anna Kirby (Prifysgol Caergrawnt)

Profi hwb integredig 1 wythnos ar yr un pryd mewn radiotherapi canser y fron: Treial Hwb FASTForward

16:00 - Egwyl lluniaeth a chyfle i edrych ar y posteri

16:30: Trafodaeth: "Mae imiwnotherapi yn ddatrysiad ar gyfer canser"

Y safonwr: Dr Martin Rolles (GIG Cymru)

Yn erbyn: Yr Athro Andy Godkin (Prifysgol Caerdydd)

O blaid: Dr Ben O'Leary (Sefydliad Ymchwil Canser)

17:10 - Gwobrau posteri a chyflwyniadau: Yr Athro Mererid Evans (Canolfan Ymchwil Canser Cymru)

17:20 - Sylwadau i gloi: Yr Athro Mererid Evans (Canolfan Ymchwil Canser Cymru)

17:30 - Derbyniad rhwydweithio a chyfle i edrych ar y posteri

About the Wales Cancer Research Centre

The Wales Cancer Research Centre is based at Cardiff University and funded by Health and Care Research Wales and our funding partners at Cardiff University, Swansea University, Bangor University, Velindre NHS Trust and Cardiff and Vale University Health Board. We work collaboratively to support cancer research across Wales and to drive progress in line with Wales’ cancer research strategy, CReSt

As part of WCRC’s role in CReSt implementation, we have opportunities for you to get involved:

*Join our bioinformatics network*

*Join our Early-Mid Career Researchers Network*

*Tap into the skills of our PPI network*

*Use our signposting resources, such as our early career researcher guide *

Sign up to our monthly newsletter to stay up to date with news, events, funding opportunities and more from the Wales Cancer Research Centre

Gwybodaeth am Ganolfan Ymchwil Canser Cymru

Wedi’illeoliymMhrifysgolCaerdydd,mae’rGanolfanYmchwilCanserCymruwedi'ihariannuganYmchwilIechyda GofalCymru,ynogystalâ'npartneriaidariannolymMhrifysgolCaerdydd,PrifysgolAbertawe,PrifysgolBangor, YmddiriedolaethGIGFelindre,aBwrddIechydPrifysgolCaerdydda'rFro.Rydymyngweithioarycydigefnogi ymchwilcanserledledCymruaciyrrucynnyddyneiflaenynunolâstrategaethymchwilcanserCymru,sefCReSt.

Mynnwchywybodaethddiweddarafdrwyein cylchlythyrigaelgwybodameinmentraua'n digwyddiadaunewydd,wrthinieucyhoeddidrwy gydolyflwyddyn Yn rhan o rôl y Ganolfan Ymchwil Canser Cymru wrth weithredu CReSt, mae sawl cyfle i chi

*Ymunwch â'n rhwydwaith biowybodeg*

*Ymunwch â’n Rhwydwaith Ymchwilwyr ar Ddechrau-Canol eu Gyrfa*

*Manteisiwch ar sgiliau rhwydwaith Cynnwys y Cleifion a’r Cyhoedd (PPI) *

* Defnyddiwch ein hadnoddau, fel ein Canllawiau i Ymchwilwyr ar ddechrau eu gyrfa *

Meet today’s sponsors

Sponsorship provided by Roche* on behalf of the Wales Cancer Industry Forum

Research and innovation drive service improvements, and Wales benefits from excellent ongoing efforts to enhance cancer prevention, diagnosis, treatment, and patient experience. The Industry Forum fosters collaboration between Industry, 3rd Sector organisations and Welsh cancer service stakeholders to improve patient care

If you are interested in learning more or getting involved, please contact wcn.r&i@wales.nhs.uk or visit: Wales Cancer Industry Forum - NHS Wales Executive

*Roche Products Ltd has provided financial support for this meeting but has had no involvement in the content

The Cardiff Cancer Research Hub is a dynamic partnership between Velindre University NHS Trust, Cardiff and Vale University Health Board and Cardiff University, working with industry, research funders and charities to deliver the next generation of cancer treatments. From bench to bedside, the Cardiff Cancer Research Hub provides a single front door to expertise and facilities spanning haematological and solid tumour cancers, from early discovery to late phase clinical trials. By increasing access to complex cancer trials in Wales and bringing together and growing an expert research workforce, we aim to translate research into better lives for people with cancer.

Velindre is the largest provider of non-surgical oncology treatment in Wales We are recognised internationally for our highly specialised services, ground-breaking and innovative research, and the expertise of our researchers. We host and sponsor a mix of commercial and non-commercial studies across a research portfolio that includes cancer clinical trials, palliative and health care research studies, as well as blood transfusion and transplantation medicine at the Welsh Blood Service. Our research enhances knowledge, leading to advances in treatments that make a difference to the care and outcomes of people with cancer in Wales and around the world.

Cancer Research Wales is the Welsh cancer research charity. Proudly independent, all of our research funding is spent in Wales, supporting talented scientists and clinicians across the country We believe in the power of research and innovation to deliver the solutions needed to improve cancer survival rates, enhance cancer patients’ quality of life and reduce inequalities.

We support a broad range of research, from innovation grants to clinical trials, across four main themes:

Discovery & Translational Research

Early Diagnosis, Prevention & Screening

Better Treatments

Health Systems & Outcomes Research

Poster and presentation awards sponsored by:

supported by Welsh Government, which brings uthorities, universities, research institutions, third ent agencies and research funders (both in Wales blic and other stakeholders. We work together to es that can lead to discoveries and innovations

Conference speakers

Conference Chair

Prof. Mererid Evans (Director, Wales Cancer Research Centre)

Professor Mererid Evans is the director for the Wales Cancer Research Centre, as well as a consultant clinical oncologist at Velindre Cancer Centre in Cardiff, specialising in head and neck cancer.

A graduate of the University of Wales College of Medicine, she received a PhD in 2001 for her research into immune responses to Human Papillomavirus (HPV) in patients with cervical cancer. Professor Evans is now chief investigator of three multi-centre clinical trials (PATHOS, Best-Of and PEARL) which all seek to develop kinder treatments for patients with head & neck cancer.

Prof. Serena Nik-Zainal (University

of Cambridge)

Serena is Professor of Genomic Medicine and Bioinformatics and an NIHR Research Professor at University of Cambridge. She is also an NHS Honorary Consultant in Clinical Genetics. Serena has pioneering expertise in cancer whole genome sequencing and big data analytics, with a particular interest in using the totality of cancer multi-omic data to fully understand cancer biology.

She was central to the development of the field of mutational signatures in cancer, uses experimental systems to validate her analytical work, and now explores other age-related progressive diseases such as neurodegeneration. Serena uses machine-learning methods to develop clinical computational tools to accelerate the translation of genomic innovations towards patients. She is the recipient of the Royal Society Sir Francis Crick Medal, Foulkes Foundation Medal and Dr Josef Steiner Cancer Research award in recent years.

Prof. Andrew Beggs (University of Birmingham)

Andrew Beggs is a Professor of Cancer Genetics & Surgery in the Institute of Cancer and Genomic Sciences, University of Birmingham. He is also the Deputy Director of the Birmingham Experimental Cancer Medicine Centre and Theme Lead for Biomarkers and Liquid Biopsy. He also is Head of Somatic Cancer in the Central and South Genomic Medicine Service Alliance. He is Co-Lead of the Translational Biology and Genetics research theme within the Institute of Cancer and Genomic Sciences. He is a fellow of the Alan Turing Institute and has recently been awarded an MRC Senior Clinical Fellowship

Currently funded by multiple industrial partners as well as the MRC, BBSRC, Sarcoma UK and Cancer Research UK, Andrew’s lab research encompasses organoid models of cancer, cancer biology and omics technologies in medicine. He is also a Consultant Colorectal & General Surgeon at the Queen Elizabeth Hospital in Birmingham with specialist interest in laparoscopic (keyhole) cancer surgery and familial cancer syndromes for which he runs as part of a national service. He is also an honorary consultant surgeon at Birmingham Children’s and Women's Hospitals.

His major research interests include solid tumour cancer biology and translational medicine. He has published articles in Nature, Nature Biotechnology, Nature Genetics, the BMJ, The Lancet, Gut, Journal of Pathology and PLoS Genetics. He collaborated in writing the European consensus guidelines for the management of PeutzJeghers syndrome. His laboratory also has interests in method development, holding the IP on long read sequencing of the Human Leucocyte Antigen (HLA) complex of genes as well as biochemical methods of sensing SNP alleles at room temperature and rapid amplification of RNA (RTF-ExPAR). During the COVID-19 pandemic he became a scientific adviser to the DSHC on COVID-19 diagnostics and is the Chief Clinician of the LFD Digital Read programme.

10:05 - 10:25

Patient and public involvement

A patient’s experience of being part of research

Bryan Webber

Bryan Webber is originally from Aberdare and qualified as a dentist in Cardiff in 1973. He spent the majority of his time in NHS general dental practice in Barry, Port Talbot and Dinas Powys. Bryan spend over 35 years as Training Programme Director for Dental Foundation Training and eventually retired in 2023 after 50 years within the NHS.

Bryan was diagnosed with tonsillar cancer in 2020 and has now completely recovered. He now acts as a patient representative for a number of organisations and talks extensively to groups within the dental profession. In his spare time Bryan is Chairman of Cardiff Male Choir and enjoys rugby and golf. Grandad duties also take up a lot of his time.

10:25 - 10:45 -

Dr Marta Williams (Cardiff University)

Precision and mechanistic oncology

Dr Marcos Quintela is a Postdoctoral Research Associate at Cardiff University, working with Dr Helen Pearson on a Prostate Cancer UK project to investigate a novel treatment for prostate cancer. He earned his PhD at Swansea University, which included a two-year placement at the Houston Methodist Research Institute in the USA After completing his PhD, he continued his research career at Swansea University as a postdoctoral researcher before joining his current position.

Immuno-oncology

Dr Marta Williams is a Postdoctoral Researcher at Cardiff University. Her PhD research into the tumour biology and mechanisms underlying cancer and adaptive immune system interactions in a mouse model of colorectal cancer led to the development of a now patented innovative cancer vaccine platform. With a strong interest in immunology and virology, Dr Williams is committed to advancing targeted viral vaccine strategies, focusing on harnessing the immune system to fight and prevent cancer.

Radiotherapy

Dr Emma Higgins (Velindre Cancer Centre)

Dr Emma Higgins is a Clinical Oncology consultant working in Velindre Cancer Centre in Cardiff She specialises in Head & Neck cancer and Skin cancer She is currently completing an MD developing Normal Tissue Complication Probability (NTCP) models to predict dysphagia following adjuvant radiotherapy treatment for HPV positive oropharyngeal cancer patients who have had surgery (as part of the PATHOS trial). She also has a role as radiotherapy quality assurance (RTQA) advisor for the PATHOS trial.

11:15 - 11:35 -

Dr Karam Aboud (All Wales Genomics Lab, Cardiff University)

Cancer clinical trials

Dr Karam Aboud is a registrar in Medical Oncology in South Wales Deanery and a clinical research fellow at the All Wales Medical Genomics Lab and Cardiff University. He is a current PhD candidate researching into resistance signatures in lung cancer using liquid biopsy.

Dr Ope Gbadegesin (Cardiff and Vale University Health Board)

Palliative and supportive oncology

Ope is currently training as an academic FY2 in Cardiff and Vale University Health Board. He has a keen interest in Oncology and hopes to pursue a career in the speciality. He hopes to start this journey by beginning IMT training this year.

Population health-based cancer prevention and early detection

Dr Tracy C. Knight (Aberystwyth University)

Dr Tracy C Knight is a Post-Doctoral Research Fellow at Aberystwyth University, specialising in translational medicine. Her PhD focused on identifying urinary biomarkers for prostate cancer using metabolomic and proteomic approaches. With expertise in clinical research coordination, project management, and point-of-care diagnostic development, she works closely with commercial and NHS partners to translate scientific innovation into practical diagnostic solutions.

11:45 - 12:50 - Breakout

Wales’ spinouts: new innovations from lab to clinic

Prof. Dean Harris (CanSense)

Prof. Dean Harris is a consultant colorectal surgeon at Swansea Bay University Health Board, subspecialising in advanced rectal cancer. He is Lead Clinician of the Colorectal ncer MDT and clinical lead for the Wales Cancer Industry Forum. He is on the NHS nical Entrepreneur Programme since 2020 fuelling his interest in MedTech innovation. 2013 he became an honorary clinical professor in Swansea University Medical School th research interests in early detection of cancer and personalised cancer treatment, dhaswonover£2Minacademicfundingtowardsthis.

He is co-founder and clinical director of CanSense, a Swansea University spin-out company, translating a reagent-free colorectal cancer serum diagnostic for the NHS to address cancer inequalities. CanSense won the St David Award for Science and Technology (2023), Wales Start-up of the year award for MedTech (2021) and the Institute ofPhysicsLeeLucasAwardforHealthcarein2021.

LinkedIn

X:@deanharris81

Prof. Alan Parker (Accession Therapeutics)

Prof. Alan Parker is Head of Solid Cancers and Professor of Translational Virotherapies, based at Cardiff University, where he has led the Viral ImmunoTherapies and Advanced therapeutics Lab (VITAL) since 2013. Prior to that, he was based at the University of Glasgow from 2005 – 2013 as a postdoc, then a Royal Society of Edinburgh Personal Fellow. He also worked previously at King’s College London (2003-2005), and his PhD was from the University of Birmingham (1998-2002). Alan’s work spans basic virology to translational oncology and involves the manipulation and engineering of adenoviruses into advanced therapeutic agents for the treatment of cancers (so called “oncolytic viruses”) The first “precision virotherapy” from the VITAL lab is licensed to Accession Therapeuticsandisduetoundergoclinicaltranslationin2025.

11:45 - 12:50 - Breakout sessions

Cancer prevention and early detection

Prof. Antonis Antoniou is a genetic epidemiologist and has made major contributions to the understanding of the genetic basis of common cancers and the development of cancer risk prediction models. Using innovative approaches to analyse data from large population-based and family studies, he has provided reliable estimates of cancer risks for carriers of mutations and BRCA1 and BRCA2 that are used every day in the clinic. His work showed that PALB2 was a high-risk breast cancer gene. He leads the coordinating centre of the international Consortium of Modifiers of BRCA1/2 and has demonstrated the importance of genetic modifiers of cancer risk for BRCA1 and BRCA2 carriers and that these modifiers lead to clinically important differences in cancer risk. He led the development of the multifactorial BOADICEA model using large-scale multimodal datasets. BOADICEA is used to predict breast and ovarian cancer risks using genetic, lifestyle, hormonal, anthropometric, and imaging risk factors. His team implemented BOADICEA into the CanRisk (www.canrisk.org) online tool used by clinicians across the world to counsel thousands of patients daily, to guide decisions on screening and surgical and medical prevention of disease. CanRisk is endorsed by clinical guidelines in several countries. He currently leads the CanRisk programme of work that aims to enable cancer risk prediction within routine frontline healthcare in the UK; and he is director of the Cancer Research UK, Cancer Data Driven Detection (CD3) national strategic initiative. He is recipient of the 2019 Basser Global Prize for “pioneering BRCA1/2 research” and the 2024 Don Listwin Award for “outstanding contributions to cancer early detection.

Dr Stephanie Smits is the Head of Population Cancer Research at the Welsh Cancer Intelligence and Surveillance Unit at Public Health Wales. Dr Smits works on a wide variety of domestic and International cancer research projects that utilise the Welsh cancer registry data. In her role, Dr Smits aims to optimize linkable data for population cancer research, leading to public and patient benefit. Dr Smits also holds an honorary contract with Cardiff University.

Dr Smits has been an active member of the cancer community in Wales since 2011. Before joining Public Health Wales, Dr Smits worked at Cardiff University on a number of cancer screening, prevention and early diagnosis projects.

Dr Stephanie Smits (Public Health Wales)

Prof. Antonis Antoniou (University of Cambridge)

13:35-14:00 -

Sponsor spotlight

The Wales Cancer Industry Forum (WCIF)

Research and innovation drive service improvements, and Wales benefits from excellent ongoing efforts to enhance cancer prevention, diagnosis, treatment, and patient experience. The Industry Forum fosters collaboration between Industry, the NHS, 3rd Sector organisations, academia and Welsh cancer service stakeholders to improve patient care In this symposium we are offering the opportunity to get involved with the forum and future partnerships and highlighting two of the key collaborations that the Forum is currently involved in. Speakers will outline developments in the clinical trials workstream of the Ministerial Initiative to Tackle Cancer, and present the innovative liquid biopsy for lung cancer research, QuicDNA and the next phase: QuicDNA Max.

Carys Thomas (Welsh Government)

Martin Coombes is the Director of Opened Door Limited, a healthcare public affairs and market access consultancy. Martin is a Senior Executive with more than 35 years’ experience in Pharmaceuticals, including many years focused on healthcare policy, government affairs, patient advocacy, NHS Relations and access to medicines With a background in sales, marketing and commercial management, Martin has an in-depth knowledge of the political, healthcare and policy environment across the UK and particularly relating to the Devolved Nations. He has a demonstrable record of success in shaping policy and in industry leadership roles.

Carys is the Head of R&D Policy at Welsh Government and oversees policy areas including NHS and social care R&D strategy and funding, industry engagement, digital and governance, and public involvement and EDI. Prior to joining Welsh Government in 2002, she worked as a senior researcher at the Home Office and has also worked in research roles at the Cabinet Office, and National Savings and Investments. Carys chairs the Tackling Cancer through Research Oversight Group in a drive to increase cancer research in NHS Wales.

Nicola is National Director of Research Support & Delivery, responsible for ensuring efficient, effective and research support and delivery across Wales (via NHS R&D offices, and national services) to ensure the seamless integration and operation of all elements to effectively support and deliver research in Wales. Nicola has worked in the NHS for 30 years and an active researcher, initially delivering research projects and programmes in primary care and public health and subsequently leading a public health research unit. Prior to her role in Wales, Nicola was Deputy Director of Research & Development in a large acute trust in England and in parallel, worked as a policy and change advisor to the Welsh and UK Governments, and the Health Research Authority. Nicola is also a Chartered Coaching Psychologist.

Dr Nicola Williams (Health and Care Research Wales)

Martin Coombes (Opened Door Limited)

13:35-14:00 -

Sponsor spotlight

Sally Spillane (All Wales Genomics Laboratory)

Dr Scrase is a Consultant Clinical Oncologist at the North Wales Cancer Treatment Centre, Lead Clinician for Radiotherapy and Joint Clinical Lead for Oncology and Senior Clinical Lecturer in Medical Education at the North Wales Medical School. He moved to Wales in July 2023 having previously worked in East Anglia at Ipswich Hospital (now ESNEFT) since November 1998. There he was a Consultant Clinical Oncologist and held a range of management and leadership roles within his own department, including Clinical Lead, Clinical Director and Divisional Director where he had management and leadership responsibility for a range of specialties. In later years, he was appointed to wider health care system roles specifically Cancer Clinical Lead reporting to the Deputy CEO of Suffolk and NE Essex Integrated Care System and joint Medical Director of the East of England Cancer Alliance. During those roles he was very much involved in linking with industry partners in innovation opportunities either via the EAHSN or through direct approaches from stakeholders This included digital prehab/rehab tools for cancer patients

He has been research-active as a consultant. This includes being principal investigator of a number of clinical trials concluding with publications as co-author on a range of practice-changing topics. He is a member of the radiotherapy arm of the EORTC and provides support to the quality assurance of clinical trials. Strategically he was chair of the Anglia (subsequently ‘Eastern’) Research Executive tasked by the NCRI to formulate a seamless research strategy for what were then two disconnected research networks within the East of England Since taking up his clinical and academic appointments in North Wales, he has also been appointed as Deputy Chair of the Head and Neck Cancer Site Group and most recently Clinical Lead for the Research and Innovation Workstream with the NHS Wales Executive.

With over 3 decades of experience in delivering genomic testing for patients in Wales, Sally currently works as the operational lead for the cancer services at the All Wales Genomic Laboratory focusing on TAT and quality targets, enabling staff development, and supporting the laboratory director and head of cancer in delivering a strategy for cancer that is key in delivering the best outcomes for patients.

A fellow of the RCPath and the Academy of Healthcare Science, Sally is also a senior examiner for the college in Genomics and an assessor for the international quality provider GENQA as well as the genomics professional lead for the welsh Healthcare Science Network. Sally is a keen Cardiff rugby supporter and loves travel and unwinding with yoga

Dr Christopher Scrase (North-Wales Cancer Centre)

14:55 - 16:00 -

Mechanistic oncology

sessions

Prof. Awen Gallimoreis a professor within the Division of Infection Immunity and CoDirector of Systems Immunity Research Institute at Cardiff University. Shegained a DPhil in Professor Andrew McMichael's laboratory in Oxford, studying the immune response to simian and human immunodeficiency viruses. With a Wellcome Trust travelling fellowship she subsequently moved to the laboratory of the Nobel laureate Professor Rolf Zinkernagel to further study factors important for anti-viral immunity.

She established her laboratory in the Nuffield Department of Medicine in Oxford to look at ways of persuading the immune system to recognise cancer. Awen moved to Cardiff in 2002 and shortly afterwards gained a senior fellowship from the MRC to expand the lab. The Cardiff lab, which currently receives funding from Cancer Research UK, Cancer Research Wales, Breast Cancer Now and The Wellcome Trust takes basic research using model systems of cancer through to testing novel immunotherapies in patients with cancer.

Assoc. Prof. Eileen Parkes is an early phase medical oncologist and associate professor at the University of Oxford. She completed her medical oncology training and PhD at Queens University Belfast before moving to Oxford in 2019. She leads early phase studies of novel immunotherapies, including STING agonists, and is lead for the Oxford Experimental Cancer Medicine Centre, focusing on translational research Her lab team studies the tumour microenvironment of chromosomally unstable cancers, with a particular focus on cGAS-STING signalling, intending to identify novel therapeutic strategies for chromosomally unstable cancers including oesophageal adenocarcinomas.

Prof. Awen Gallimore (Cardiff University)

Assoc. Prof. Eileen Parkes (University of Oxford)

14:55 - 16:00 -

Breakout sessions

Clinical Trials

Krishna is a Professor of Urology at Cardiff University and Consultant Urologist at the University Hospital of Wales in Cardiff. He is the Chief Investigator for the NIHR ELIPSE study and holds several grants on multi centre UK trials as a collaborator. He eads Cardiff University’s Urology multidisciplinary research group with personal nterest in optimising cancer diagnostics, biomarker and clinical trials-based research. Over the last 15 years, he has led significant improvements urological cancer services in South Wales and served as the Chair of BAUS Oncology (British Association of Urological Surgeons), NICE Prostate Cancer guidance committee and the NPCA (National Prostate Cancer Audit)

Dr Anna Kirby is a Consultant Clinical Oncologist specialising in the treatment of patients with breast cancer. She leads research into novel breast radiotherapy techniques at The Royal Marsden and Institute of Cancer Research, London. She is Chief Investigator of FAST-Forward Boost, Technical Radiotherapy Lead for the PARABLE Proton Trial, Chief Clinical Co-Ordinator for the IMPORT breast radiotherapy trials and Breast Lead on the CORE trial evaluating the role of stereotactic radiotherapy in treating metastatic disease

Dr Kirby graduated from Cambridge University in 1995 with a first-class honours degree in Medicine and Psychology. Her specialist oncology training was completed at The Royal Marsden and Guy's and St Thomas' Hospitals following which she undertook a research degree at the Institute of Cancer Research. Her publications describe methods for improving the accuracy of breast cancer radiotherapy and for reducing late side-effects of treatment including heart disease Alongside colleagues, her work in heart-sparing breast radiotherapy, partial breast radiotherapy and simultaneous integrated boost treatment has changed international practice.

Dr Kirby was President of the European Society of Radiation Oncology (ESTRO) from 2022-24 and remains a member of the ESTRO Board.

Professor Krishna Narahari (Cardiff and Vale University Health Board)

Dr Anna Kirby (The Royal Marsden NHS Foundation Trust & Institute of Cancer Research)

16:30 - 17:10 -

Debate speakers

Prof Andrew Godkin Andrew took up a position as a consultant physician and hepatologist in the University Hospital of Wales in Cardiff in 2002, and was made a Reader in Cardiff University in 2008, and then received a chair in 2014. His continuing research activity has centred on understanding how the immune system attacks cancer, and how this knowledge can be used for designing new treatments. Based on research activity since arriving in Wales, he has completed a vaccine trial for patients with advanced colorectal cancer, and is now launching a multi-centre trial looking at immunomodulation in CRC patients, who have completed treatment, aiming to prevent recurrence.

Dr Ben O’Leary (Institute of Cancer Research)

Dr Martin Rolles

South-West Wales Cancer Centre, Swansea

Dr Ben O’Leary is a Clinician Scientist and Group Leader at The Institute of Cancer Research and an Honorary Consultant in Clinical Oncology at The Royal Marsden. His research is focused on understanding the evolution of resistance to cancer therapies in head and neck cancers, including the use of liquid biopsies. He leads several translational studies and clinical trials at The Institute of Cancer Research and The Royal Marsden.

Dr Martin Rolles is a Clinical Oncologist specialising in Head & Neck Cancer, and NonMelanoma Skin Cancer Martin read medicine at the University of Wales. Following specialist training in Wessex and Vancouver, Martin returned in 2006 to take up his consultant post at the South West Wales Cancer Centre in Swansea. He is chair of the Welsh Scientific Advisory Committee. He also chairs the Wales Cancer Network Clinical Reference Group, and the All-Wales PBT, PET, and Molecular Radiotherapy Advisory Groups Martin is committed to clinical research and has been Principle Investigator for a number of multicentre national and international trials. He is part of an active research group using linkage of large national datasets to understand inequalities in cancer diagnosis and outcomes.

Prof. Andrew Godkin (Cardiff University)

The Cancer Research Strategy for Wales (CReSt)

The abstracts, posters and oral abstract presentations within the conference are aligned with the themes in CReSt, Wales’ first national cancer research strategy.

Precision and mechanistic oncology

Looking at how genetics can affect who gets cancer, how that cancer behaves, and finding ways to treat cancers with particular genetic 'signatures'.

Cancer clinical trials

Bringing promising new treatments to patients in trials and testing new ways of giving existing treatments.

Immuno-oncology

Understanding how our bodies' immune responses change when cancer develops, and finding ways to use the immune system to help fight cancer.

Palliative and supportive oncology

Finding the best ways to look after patients with cancer, such as pain control, side effect management and mental health support.

Radiotherapy

Exploring how radiotherapy can kill cancer cells while limiting the impact on the rest of the body.

Prevention, early detection, primary care and health services research

Finding new ways to prevent cancer and detect it early, and making sure that health services in Wales are underpinned by strong science.

The CReSt themes are areas where Wales shines already, and by working together and focusing our efforts we can achieve even more. This maximises research opportunities for patients and ensures we keep learning and applying new advances within and beyond the clinic. Everyone involved in cancer research in Wales has a part to play in making the CReSt strategy become a reality, and we hope this day will inform, inspire and motivate you along your journey.

Strategaeth Ymchwil Canser Cymru (CReSt)

Mae’r crynodebau, y posteri a’r cyflwyniadau llafar o grynodebau yn y gynhadledd yn cyd-fynd â’r themâu yn CReSt, strategaeth ymchwil canser genedlaethol gyntaf Cymru.

Oncoleg fecanistig a manwl-gywir

Edrych ar sut y gall geneteg effeithio ar bwy sy'n cael canser, sut mae'r canser hwnnw'n ymddwyn, a chanfod ffyrdd o drin canserau â 'llofnodion' genetig penodol.

Treialon clinigol ym maes canser

Dod â thriniaethau newydd addawol i gleifion mewn treialon a phrofi ffyrdd newydd o gynnig triniaethau presennol.

Imiwno-oncoleg

Deall sut mae ymatebion imiwn ein cyrff yn newid pan fydd canser yn datblygu, a dod o hyd i ffyrdd o ddefnyddio'r system imiwnedd i helpu i frwydro yn erbyn canser.

Oncoleg gefnogol a lliniarol

Dod o hyd i'r ffyrdd gorau o ofalu am gleifion â chanser, fel rheoli poen, rheoli sgîl-effeithiau a chymorth iechyd meddwl.

Radiotherapi

Ystyried sut y gall radiotherapi ladd celloedd canser tra'n cyfyngu ar yr effaith ar weddill y corff.

Ymchwil yn ymwneud ag atal, canfod cynnar, gofal sylfaenol a gwasanaethau iechyd

Dod o hyd i ffyrdd newydd o atal canser a’i ganfod yn gynnar, a gwneud yn siŵr bod gwasanaethau iechyd yng Nghymru yn cael eu hategu gan wyddoniaeth gref.

Mae themâu CReSt yn feysydd lle mae Cymru'n rhagori ynddynt eisoes, a thrwy gydweithio a chanolbwyntio ein hymdrechion, gallwn gyflawni mwy hyd yn oed. Bydd hyn yn caniatáu i gleifion fanteisio i’r eithaf ar gyfleoedd ymchwil a sicrhau ein bod yn parhau i ddysgu o’r datblygiadau newydd a welir o fewn a thu hwnt i'r clinig, a’u cymhwyso. Mae gan bawb sydd ynghlwm ag ymchwil canser yng Nghymru ran i'w chwarae wrth wireddu'r strategaeth CReSt ac rydym yn gobeithio y bydd y diwrnod hwn yn ddefnyddiol, yn eich ysbrydoli ac yn eich ysgogi hyd eich taith.

Lightning talk abstracts

Theme 1: Precision and mechanistic oncology

Exploration of predictive biomarkers for BCL3 inhibitor treatment response in advanced prostate cancer

Marcos Quintela-Vazquez1, Tabitha Cunliffe1, Daniel J Turnham1,2, Anna E Richards1, Wytske van Weerden3, Robert Jones4, Andrew D Westwell5, Richard Clarkson1, Helen B Pearson1

1. European Cancer Stem Cell Research Institute, School of Biosciences, Cardiff University

2. School of Applied Sciences, University of the West England (UWE) Bristol

3. Experimental Oncology, Erasmus University Rotterdam

4. School of Medicine, Cardiff University. 5. School of Pharmacy, Cardiff University

Prostate cancer (PC) is the second leading cause of cancer-related mortality in men. While early-stage localised PC is effectively managed, relapsed disease can advance to incurable metastatic castrationresistant PC (mCRPC) following hormone therapy resistance. With a 5-year survival rate of <30%, novel therapies are urgently needed. The oncogenic NF-kB signaling pathway is frequently upregulated in PC/mCRPC, however, existing NF-kB inhibitors harbour tolerability/efficacy issues. To address this, we developed TNAT-101, a well-tolerated small molecule inhibitor of BCL3 that disrupts BCL3:NF-kB interactions to supress NF-kB signaling. Preliminary studies evaluated the efficacy of TNAT-101 in the androgen receptor positive patient-derived xenograft PC2400 mCRPC model, treated with TNAT-101 (10mg/kg) or vehicle for 20 days (n=3/group). TNAT-101 significantly reduced tumour burden without overt side effects, demonstrating excellent tolerability and efficacy. However, the mechanistic basis of BCL3 inhibition (BCL3i) and predictive biomarkers for patient stratification remain unclear. To explore BCL3i mechanisms and identify biomarkers of sensitivity, we performed RNA-Seq on TNAT-101 and vehicle-treated samples. RNA-Seq data was processed using STAR and DESeq2, identifying 355 differentially expressed genes (FDR<0.05). Pathway analysis indicated that alterations in extracellular matrix (ECM) components are associated with BCL3i. Candidate predictive markers for BCL3i sensitivity include VCAN, a major ECM component, and CMKLR1, a negative regulator of NFkB, both up-regulated >10-fold. While future work is needed, these findings provide valuable insights into the mechanistic pathways modulated by BCL3. Altogether, our results underscore the therapeutic potential of TNAT-101, indicating BCL3i as a promising new therapy for mCRPC that is urgently needed in the clinic.

Funder acknowledgement: Prostate Cancer UK

Theme 2: Immuno-oncology

An adenovirus-based 5T4-expressing cancer vaccine induces inflationary CD8+ T cell responses that afford protection from colorectal cancer

Dr Marta Williams1, Dr Sandra Dimonte1, Morgan Marsden1, Lucy Chapman1, Dr Evelina Statkute2, Prof Andrew Godkin1, Prof Richard J Stanton1, Prof Awen Gallimore1, Prof Ian R Humphreys1

1. Cardiff University

2. Oxford Biomedica

There is increasing evidence suggesting that immune cells such as T cells can be exploited to promote protection from tumours. Anti-cancer vaccines have the potential to harness anti-tumour T cell responses to limit cancer development and have recently regained significant interest as exciting therapeutic targets. Nonreplicating adenoviral-based vaccine vectors have been extensively evaluated and, in the context of COVID-19, exploited broadly due to their ease of genetic manipulation, safety profile and ability to elicit robust immune responses, including CD8+ T-cell responses. The prevailing immunisation strategy with antigen-based cancer vaccines is to incorporate tumour-associated antigens as therapeutic targets. Colorectal cancers are highly enriched for expression of the tumour associated antigen 5T4.

Patients with primary colorectal cancer undergo surgical resection with adjuvant chemotherapy but postsurgery chemotherapeutics offer benefit to only 15-25% of patients, with substantial toxicity and remaining risk of a relapse. There are currently no proven interventions in this group to prevent relapse and using a vaccination approach is an attractive concept. Here we show that immunisation with adenoviral vectors expressing an individual epitope from 5T4 induces large expansions of 5T4-specific T-cell responses. These vaccine-induced T-cell responses were maintained at high frequencies over time and lacked features of T cell exhaustion. Our results also demonstrated that these vaccine-induced T-cells restricted microadenoma development in a mouse model. Overall, this study demonstrates the ability of adenoviral-based vectors to induce protective anti-tumour T-cell responses against an endogenously expressed tumour-associated antigen and implies the exciting potential of exploiting these approaches in cancer vaccination strategies.

Funder acknowledgement: GW4 BioMed MRC Doctoral Training Partnership, MRC Confidence in Concept

Theme 3: Radiotherapy

Abstract Contents

Development of a Normal Tissue Complication Probability Model for Dysphagia in PATHOS trial patients

Emma Higgins1, Richard Webster1, Nachi Palaniappan1, Chris Hurt2, Zohal Nabi3, Kostas Rizos3, Riki Lad3, Kate Elliott3, Elizabeth Miles3 , Joanne Patterson4, Kate Hutcheson5, Joanne Canham2, Lizette Nixon2, Christie Heiberg2, Matt Beasley6, Jones T7, Evans M1,8

1. Velindre Cancer Centre, Directorate of Medicine, Cardiff, United Kingdom

2. Centre for Trials Research, Cardiff University, Cardiff, UK

3. National Radiotherapy Trials Quality Assurance Group, Mount Vernon Cancer Centre, UK

4. School of Health Sciences, University of Liverpool, Liverpool, United Kingdom

5. Division of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, USA

6. University Hospitals Bristol NHS Foundation Trust, Bristol Haematology and Oncology Centre, Bristol, UK

7. Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, United Kingdom

8. Division of Cancer and Genetics, School of Medicine, Cardiff University, Cardiff, United Kingdom

Purpose

To develop a Normal Tissue Complication Probability (NTCP) model to identify patients at higher risk of dysphagia following transoral surgery and adjuvant radiotherapy.

Material/Methods

The dataset included 116 patients allocated into arms B1 & C2 of the PATHOS trial from Jul 2007 to Feb 2020. The model dysphagia endpoint was MDADI composite score <80 at 12months post treatment (MDADI_12m). Candidate predictors included mean dose to nine swallowing OARs (SWOARs). To develop the model, a multivariate logistic regression analysis with stepwise backward elimination was used. Model performance was evaluated by discrimination (area under the receiver operating curve (AUC)) and calibration (calibrationin-the-large (CITL); calibration slope (C-slope)).7 Internal validation was completed using bootstrapping. Statistical analysis was conducted using Stata© software (version 17.0 SE, statacorp).

Results

Mean doses to the PCM_Superior and Larynx_SG were most predictive for MDADI_12m. The risk of MDADI_12m <80 can be estimated using the model equation: NTCP MDADI_12m = 1/(1+ e-S), where S= -5.99 + (mean dose PCM Superior x 0.086) + (mean dose Larynx_SG x 0.035). The AUC, CITL and C-slope were 0.66, -0.003 and 0.73 respectively indicating good performance in terms of discrimination. However the C-slope of 0.66 suggests a moderate amount of shrinkage is required to adjust the predictor effects in the model for overfitting.

Conclusion

This novel NTCP model could be used to direct limited resources (e.g speech and language therapy) to patients who are at highest risk of dysphagia following surgery and adjuvant radiotherapy, as well as in treatment planning to prioritise SWOAR optimisation.

Funder acknowledgement: Funded by Cancer Research UK (Grant no: A25317), co-sponsored by Cardiff University and Velindre University NHS Trust.

Theme 4: Cancer clinical trials

Dendrimer-Nanoparticle (DEP) Delivery of Cabazitaxel (DEP-Cabazitaxel): a first-in-human Phase 1/2 Trial in Patients With Advanced Solid Tumors

Karam Aboud, MBChB1, David J. Pinato, MD, PhD2,3, Martin D. Forster, MBBS, PhD4, Anthony M. Joshua, MBBS, PhD5, James Korolewicz, MBBS2,6, Cienne Morton, MBBS8, Jia Liu, MD PhD5, Rasha Cosman, MBBS5, Nicola J. Main, BPharm7, Julia Le Meur, MSc7, Jeremy R.A. Paull, PhD7, Stephanie R. Edmondson, PhD7, James Spicer, FRCP, PhD8, Robert H. Jones, MBBS, PhD1

1. Velindre Cancer Centre and Cardiff University, Cardiff, UK

2. Department of Surgery & Cancer, Imperial College London, London, UK

3. Department of Translational Medicine, Division of Oncology, University of Piemonte, Novara, Italy

4. University College London (UCL) Cancer Institute, UCL Hospital NHS Trust, London, UK

5. The Kinghorn Cancer Centre, St Vincent’s Hospital, Sydney, NSW, Australia

6. University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, UK

7. Starpharma Pty Ltd, Abbotsford, VIC, Australia

8. King’s College London, Guy’s Hospital, London, UK

Background

DEP CTX is an optimized dendrimer nanoparticle formulation of cabazitaxel that achieves sustained cytotoxic drug delivery to tumors via enhanced permeability & retention effects. Unlike standard cabazitaxel (s-CTX), DEP CTX does not contain toxic excipients associated with anaphylaxis requiring steroid/antihistamine premedication. We report the final Phase 2 efficacy and safety results in advanced/metastatic solid tumor patients.

Methods

DEP CTX was given at 20 mg/m2 cabazitaxel, IV 3-weekly. Efficacy was assessed radiologically and by tumour markers.

Results

75 pts were enrolled, prioritizing metastatic castration-resistant prostate, esophagogastric & ovarian cancers. Median progression free survival (mPFS) and overall survival (mOS) were 3.8 and 9.0 mths, respectively. Objective response rate (ORR) was 20%. All 25 mCRPC pts had a median of 4 prior lines of anticancer treatment. mPFS was 4.4 mths, mOS was 14.7 mths. The disease control rate (DCR) was 70.6%; ORR was 16.7%. PSA reduced in 90% pts. For 15 esophogogastric patients mPFS was 4.0 mths, mOS was 8.6 mths. Overall, DCR was 80%; ORR 30%. Of 22 ovarian pts, 96% were platinum resistant with a median of 4 prior lines of anticancer treatment, mPFS/mOS were 3.1 mths & not reached respectively. DCR was 66.7%; ORR 17.6%. Treatment related adverse events were mostly mild/moderate.

Conclusions

DEP CTX exhibited clinically meaningful, durable antitumor activity in advanced solid cancers without the need for steroid premedication. The antitumor activity & safety results compare favorably to s-CTX, or standard of care chemotherapy in non-prostate cancers highlighting the promising potential of dendrimer-enhanced delivery of cabazitaxel.

Funder acknowledgement: This study was funded and sponsored by Starpharma Pty Ltd.

Theme 5: Palliative and supportive oncology

Fracture Related Hospital Admissions in Patients with Metastatic Castrate Resistant Prostate Cancer (mCRPC) Treated with Radium - 223 Dichloride

Ope Gbadegesin1, Jake Tanguay2

1. FY2 Doctor, Cardiff and Vale University Health Board

2. Consultant Clinical Oncologist, Velindre Cancer Centre

Introduction

Radium-223 recommended by NICE since 2016 for the treatment of adults with metastatic castration-resistant prostate cancer delivers high-energy alpha particle radiation to bone metastases causing localised cytotoxic effects. Patients are commonly prescribed oral or IV bisphosphonates to reduce the likelihood of skeletal events. The PEACE III trial by Gillessen et al. presented at ESMO 2024 showed that treatment with boneprotecting agents reduced the 12-month cumulative incidence of fractures from 37.1% to 2.7% in the enzalutamide plus radium-223 arm. In this study we compare the incidence of skeletal events in patients receiving treatment with Radium-223 and given either IV or oral bisphosphonates.

Methods

Retrospective data collection, including 74 patients with mCRPC treated with radium-223 between May 2019 and March 2024. Primary measures were time to skeletal event and 12-month incidence of fracture related hospitalisations.

Results

The median overall survival was 16.7 months. Median time to skeletal event was 57 months in the IV group compared to 29 months in the oral group. The 12-month incidence of fractures requiring hospitalisation was 29.3% and 9.1% for IV and oral bisphosphonates respectively.

Conclusion

In this study the median overall survival reflects the ALSYMPCA trial findings (14.0 months). Despite the IV group demonstrating a longer median time to skeletal event, they had a higher 12-month incidence of fracture related hospitalisations than the oral group. This study highlights the high risk of fractures even with bisphosphonates and supports early proactive interventions for bone health in metastatic prostate cancer.

Funder acknowledgement: NA

Theme 6: Population health-based cancer prevention and early diagnosis

Changes in the urinary proteome could differentiate between prostate cancer and benign prostatic hyperplasia

Tracy C. Knight1, Nur Aimi Aliah Zainurin1, Russell Morphew1, Edward Hughes1, David Rooke2, Stephen F. Hughes3, Iqbal Shergill4, NS Luis A. J. Mur1

1. Department of Life Sciences, Aberystwyth University

2. ProTEM Services Ltd

3. Maelor Academic Unit of Medical and Surgical Sciences, Gwenfro Buildings, Wrexham

4. The Alan de Bolla Wrexham Urology Unit at Wrexham Maelor Hospital, Wrexham

Introduction

Prostate specific antigen (PSA) levels and digital rectal examination (DRE) are established first pass screens for prostate cancer (PCa). However, both methods show poor sensitivities and specificities.

Aim

To assess if proteomic approaches can reveal diagnostically relevant changes in urine from men with PCa compared to Benign Prostatic Hyperplasia (BPH) and symptom controls (SC).

Methods

50 urine samples (20 PCa [Gleason Scores ≥ 7], 20 BPH, 10 Symptom Controls [SC]) were assessed by proteomics approaches. Purified urinary proteins were trypsin digested and profiled by Liquid chromatography–tandem mass spectrometry (LC-MS/MS). The protein identifications and abundances were generated using Thermo ScientificTM Proteome DiscovererTM software. Results were interrogated by partial least square – discriminant analyses (PLS-DA), whilst Receiver Operating Characteristic Curve (ROC) values were used to suggest diagnostic accuracies.

Results

PLS-DA suggested urinary proteins from PCa patients were distinctive from those of BPH and SC. ROC analysis suggested the top 5 major sources of variations could discriminate between PCa and BPH with > 90% accuracies. The key proteins included a delta(14) sterol reductase, semenogelin2, a tubulin specific chaperone C, mucin-5AC and a receptor type tyrosine protein phosphatase and epidermal growth factor receptor kinase.

Conclusions

This pilot study suggests that urine proteins could be used to distinguish between BPH and PCa. The key protein differences suggest changes in steroid processing and signalling events linked to cellular proliferation, which are known features of PCa. If substantiated by further studies these protein changes could be used to detect PCa in a urine-based test.

Funder acknowledgement: NA

Poster abstracts

Theme 1: Precision and mechanistic oncology

Theme 1, Abstract 1

Unveiling the heterogeneity of pancreatic cancer initiation: a novel perspective on normal-mutant cellcell Interactions

Ella Reed1, Catherine Hogan1 , Beatriz Salvador-Barbero1

1. ECSCRI, School of Biosciences, Cardiff University, Cardiff, UK

Pancreatic cancer (PC) is a devastating disease with abysmal survival rates, due to late diagnosis and early metastasis. Understanding PC development is crucial to identify biomarkers of early disease and prevent its progression. In most cases, PC initiates from KRAS mutant cells. These cells induce permanent acinar-toductal metaplasia (ADM). KRAS mutant cells drive the progression of ADM to pancreatic intraepithelial neoplasias (PanINs). Accumulation of other genomic alterations drive PanINs progression to invasive carcinoma. Our preliminary data, using a mouse model that more accurately mimics sporadic disease by activating KRas mutations only in few cells of the pancreatic epithelium, unearthed the presence of nonmutant cells in PC initiation. This suggests a collaboration between non-mutant and KRas mutant cells in PanINs and tumours. By analysing banked mouse tissue, we demonstrate how the 3D distribution of KRas mutant cells changes through neoplastic lesion development and tumour progression, unveiling mixed populations of mutant and non-mutant cells within PanINs and tumours. The transition from low-grade to high-grade PanIN is accompanied by an increase in non-mutant cells neighbouring mutant cells, suggesting a dynamic interplay between the two is required for tumour progression. We also unravel the heterogeneity of KRas wildtype and mutant cells in the same neoplastic lesion using BaseScope, confirming the presence of both KRas mutant and non-mutant cells. We therefore hypothesise that KRAS mutant cells recruit non-mutant cells to PanINs to utilise them as support for lesion development.

Funder acknowledgement: Pancreatic Cancer UK

Theme1,Abstract2

AbstractContents

Understandingthe unctionalimportanceo theWntreceptorFZD7inprostatetumourigenesis

JesscaHembrough1,KeranHodson1 ,TobyPhesse1,HelenPearson1

1. EuropeanCancerStemCellResearchInsttute,Card Unvers ty

Prostatecancer sthesecondmostcommoncancer nmen,contrbutngto375,000deathsannually.In prostatecancer,aberrantactvatono Wntsgnallng s nvolved ntumour ntaton,progresson,metastass andtherapeutcresstance.Mutatons ncoreWntpathwaycomponents(APCand β-catenn)areless requent nprostatecancer, nsteadderegulatonarsesthroughalteredexpressono Wntlgandsandreceptors. Frzzled(FZD1-10)receptorsarememberso theGproten-coupledreceptor amly,servngasprmary receptors ntheWntpathway,thatmedateproleraton,derentaton,mgraton,apoptossandstem-cell mantenance.LteraturehasshownFZD7-medatedWntsgnallng nuencesprogressonandmetastasso gastrc,colorectalandovarancancer.Howeverthe unctonal mportanceandtherapeut cbeneto targetng FZD7 nprostatecancerhasnotbeenexplored.Prevousstudes nourlabhavedemonstratedthatprostate cancercellshavean ncreasedexpressono FZD7,comparedtonormalprostatecells.Theamo ths research stoelucdatetheroleo FZD7 nearlyprostatetumourgeness,and nvestgate ts nvolvement n the nteractonbetweenprostatecancercellsandCancer-AssocatedFbroblasts(CAFs).Thswllbeach eved byacombnatononvtroand nvvostudeswthFZD7overexpressngandknockdownnormalprostateand prostatecancercells.Addtonallyaco-culturemodelo prostatecellsand broblastsw llbeestablshedto examnetheroleo FZD7durngcell-to-broblast nteractons.Thsstudyhopestoenhancethe unctonal andmolecularunderstand ngo FZD-medatedWntsgnall ngdurngprostatetumourgeness,andprovdea noveltherapeutctarget nprostatecancer.

Funderacknowledgement:NA

Theme 1, Abstract 3

Abstract Contents

Developing Small Molecule Inhibitors of GATA2: a novel approach to target leukaemia blasts and stem cells in therapy-resistant acute myeloid leukaemia

Rebekah

Clarke1,3, Neil Rodrigues2, Gui Feng2, Marcella Bassetto3 , Salvatore Ferla1

1. Medical School, Pharmacy, Grove Building, Swansea University, SA2 8PP

2. European Cancer Stem Cell Research Institute, Cardiff University, School of Biosciences, Maindy Rd, Hadyn Ellis Building, Cardiff CF24 4HQ

3. School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Redwood Building, King Edward VII Avenue, Cardiff, CF10 3NB

Acute Myeloid Leukaemia (AML) is an aggressive blood cancer characterised by the excess proliferation of abnormal leukaemic blast cells (LBCs), due to the inability of myeloid progenitor cells to differentiate into specialised blood cell types. Annually, AML accounts around 2,700 deaths in the UK. Standard treatments, such as high-dose chemotherapy, often lack specificity and are highly toxic, resulting in a poor prognosis. A major challenge in AML treatment is the presence of leukaemic stem/initiating cells (LSCs), which account for relapse in AML patients. We have focused our research effort on GATA2, a transcription factor overexpressed across 25% of all AML cases. Our research group has previously identified a hit molecule which promotes apoptosis in myeloid leukaemia cell lines, and on the relapse propagating LSCs, while sparing Gata2 knockout LSCs, indicating the specificity of our molecule to inhibit GATA2. We have designed, synthetised, and biologically evaluated a series of 29 analogues of the hit compound, to determine an initial structure activity relationship (SAR), aiming to develop more potent and selective GATA-2 inhibitors. These analogues have shown promising ability to stop cell proliferation, and induce apoptosis, in a dose-dependent manner, more potent than the hit, with IC50 in the range of 4.9 to 25 µM, in different leukaemia cell lines. Structural optimisation cycles, which aim to further improve the activity, potency and pharmacokinetic profile of our compounds, are ongoing. These results represent a basis for the development of first, novel, selective GATA2 inhibitors able to target both LBCs and AML propagating LSCs.

Funder acknowledgement: Cancer Research Wales

Theme 1, Abstract 4

Abstract Contents

Targeting The WNT Ligand Receptor Complex in Cholangiocarcinoma and Prostate Cancer: Therapeutic Potential of FZD7-ADC and WNT974 in Metastatic Disease

Kieran Hodson1, Hector Arredondo2, Valerie Meniel1, Aled Clayton3 , Toby J Phesse1

1. Cardiff University School of Bioscience, European Cancer Stem Cell Research Institute

2. The University Of Sheffield, The Mellanby Centre for Musculoskeletal

3. Cardiff University, School of Medicine

Wnt Pathway deregulation or overexpression has been demonstrated in many cancer types, including cholangiocarcinoma (CC) and prostate cancer (PC). Despite low Wnt pathway mutation frequencies in CC, patients commonly present with advanced metastatic disease, characterized by elevated Wnt signalling activity and poor clinical outcomes. Alternatively, PC exhibits ligand-receptor level deregulation in metastatic cases. Both cancers show increased expression of the Wnt receptor FZD7, contributing to treatment resistance and disease progression. We investigated the therapeutic potential of targeting Wnt ligand release and FZD7 receptor activity using WNT974 (a porcupine inhibitor) and a novel FZD7-ADC (FZD7 specific mono-clonal antibody conjugated to MMAE). In vitro assays assessed Wnt signalling’s role in metastasis in PC and CC cells. In vivo, WNT974 and FZD7-ADC significantly reduced CC peritoneal metastases, while only FZD7-ADC was effective against CC liver metastases. Importantly, FZD7-ADC also targeted established liver metastases, reflecting a clinically relevant scenario. Additionally, depleting extracellular vesicles reduced colony formation and migratory capacity of CC cells, suggesting a role for the metastatic niche in cancer progression. Ongoing in vivo studies aim to validate these findings in PC. Our results highlight FZD7-ADC as a promising therapeutic strategy for treating CC metastases and potentially PC.

Funder acknowledgement: Prostate research conducted under a Prostate Cancer Research (PCR) grant & Cholangiocarcinoma research funded short term via Cardiff University DEVAR Cancer innovation grant

Theme 1, Abstract 5

OmicsChart: Multi-Omics Cancer Biomarker Discovery for Translational Researchers

Asta Vasalauskaite1 , Tatsiana Aneichyk1

1. OmicsChart Tech Ltd

Abstract Contents

OmicsChart is Cardiff based bioinformatics startup dedicated to addressing challenges in translational cancer research. Our mission is to simplify access to harmonized biomarker data by integrating public, proprietary, and in-house datasets. Currently, we manage over 24,000 case records from cancer patients sourced from 30 providers and 70+ studies, spanning four multi-omics modalities: RNA-seq, genomics, single-cell RNA-seq, and MS proteomics. These resources are continuously expanding to meet the evolving needs of researchers. Our software platform supports analysis of DNA and RNA biomarkers, immune cell composition, and single-cell tumor resolution, all linked with clinical data from 37 cancer types. With user-friendly scientific visualizations and standardized workflows, we enable researchers to perform complex analyses efficiently, reducing data acquisition and analysis times compared to traditional approaches. In addition to providing access to comprehensive datasets, we offer tailored bioinformatics services to global pharmaceutical clients, supporting their translational oncology teams in hypothesis testing, biomarker discovery, and data-driven decision-making. Backed by seed funding from Swiss pharma Debiopharm Innovation Fund and a research grant from Merck KGaA, we are committed to accelerating cancer research and innovation in cancer bioinformatics.

Funder acknowledgement: NA

Theme 1, Abstract 6

Developing

and

Abstract Contents

evaluating a virtual laboratory to support medical student oncology education

Karen R Reed1, Owen J Crawford2, Hannah D West1 , Joseph Lewis3, Michael Hackman2, Andreia de Almeida1, Andrew Hilbourne2, Emma Short4, Sarju Patel1, Keith Hart1 , Athanasios Hassoulas1

1. Centre for Medical Education, School of Medicine, Cardiff University, Cardiff, CF14 4YU, UK

2. Cardiff Learning & Teaching Academy, Cardiff University, Cardiff CF10 3AT, UK

3. Department of Cellular Pathology, University Hospital of Wales, Cardiff, CF14 4WX, UK

4. Swansea Bay University Health Board, Morriston Hospital, Swansea, SA6 6NL

Engagement with and understanding of the topics of genetics and histopathology, that is the study of our genes and the diagnosis and study of disease in tissues, are important aspects of oncology teaching that students have historically found difficult. We have developed a novel virtual laboratory e-learning resource (henceforth the VR-lab), that uses an interactive 3-dimentional platform to deliver the core teaching content of this tricky topic.

Using the VR-lab, students follow the journey of a patient sample, exploiting the benefits of narrative pedagogy. This content was based on a pre-existing workshop that was previously delivered using a workbook and a flipped classroom approach. Whilst maintaining the flipped classroom, the VR-lab has improved the experience of student engagement in the workbook content. 85% of students rated the VR-lab engaging, compared to 30% for the workbook.

Here we will outline the process of developing the VR-lab, highlighting the timescales and workload involved, as well as providing an overview of the resource, the initial evaluation results and student feedback. It is our hope, that by sharing this story, we can inspire and support others to use this technology to support learning and improve student experiences, inspiring the next generation.

Funder acknowledgement: NA

Theme 1, Abstract 7

Abstract Contents

Cancer Chemotherapy Curability is Determined by On Going Developmental Epigenetic Processes

1

Philip Savage

1. Dept of Medical Oncology, Cardiff University

Introduction

Whilst the majority of metastatic cancers remain resistant to curative drug treatment, a number of rarer malignancies, comprising gestational choriocarcinoma, testicular cancer and ovarian germ cell tumours, acute lymphoblastic leukaemia, high grade lymphoma, Hodgkin’s disease and some of the childhood malignancies have been routinely curable with cytotoxic chemotherapy drugs for more than 50 years. The explanation for this dramatic divergence in curability between these relatively rare malignancies and the more common incurable metastatic malignancies has long been a subject of great interest and scientific debate.

Hypothesis

Recently we have suggested that a key central component determines heightened chemotherapy sensitivity and cancer curability. This is the persistence in the malignant cells of the naturally heightened apoptotic sensitivity that their usually transient cells of origin hold at the time of their malignant transformation. Whilst the genetic event of mitosis is common to all human cells, the chemotherapy curable malignancies each appear to have a very close temporal association between their cells of origin and the biologically specialised epigenetic events occurring in them. These epigenetic events are nuclear fusion (trophoblast tumours), immunoglobulin VDJ gene recombination (acute leukaemia), immunoglobulin gene somatic hypermutation and class switching (high grade NHL), meiosis (germ cell tumours) or gastrulation (childhood malignancies).

Discussion

We will discuss these key epigenetically driven events occurring in the cells of origin at the time of malignant transformation and how these unique pro-apoptotic phenotypes are preserved in these malignancies. These processes plus the absence of any hierarchical cancer stem cells makes these malignancies highly sensitive to DNA damaging chemotherapy and may provide alternative pathways that can be targeted for less toxic therapy development.

Funder acknowledgement: NA

Theme 1, Abstract 8

Abstract Contents

Discovery of first-in-class BCl3-p50 protein-protein interaction inhibitor for the treatment of advancedstage breast cancer

Dusan Ruzic1, Carwyn Hughes2, Arwyn Jones1, Richard Clarkson2, Andrea Brancale3 , Andrew Westwell1

1. Cardiff University, School of Pharmacy and Pharmaceutical Sciences, Cardiff, Wales, U.K.

2. Cardiff University, European Cancer Stem Cell Research Institute, Cardiff, Wales, U.K.

3. University of Chemistry and Technology, Prague, Czech Republic

The BCL3 protein is an oncogenic driver that regulates the NF-κB transcription factor pathway, thereby stimulating the metastatic spread of breast cancer cells. Recent studies have highlighted the role of BCL3 in modulating the WNT/β-catenin signaling pathway in advanced colorectal cancer models1. In this study, we present the discovery and preclinical development of the first BCL3-p50 protein-protein interaction inhibitor (compound JS6). A computer-aided drug discovery pipeline developed in our laboratory, combining virtual screening and molecular dynamics simulations, led to the identification of this novel inhibitor targeting the BCL3-p50 interaction. The identified compound, an anthranilic acid derivative (JS6), met our initial product profile criteria, including anti-metastatic activity in an in vivo breast cancer model. As a non-cytotoxic compound, JS6 was found to significantly suppress NF-κB signaling, tumor colony formation, and cancer cell migration2. Furthermore, JS6 could be encapsulated in targeted PLGA nanoparticles to enhance dual drugtargeting activity in HER-2-expressing breast cancer cell models. Further structural optimization of JS6 led to the development of the orally bioavailable clinical candidate, TNAT-101. Compound TNAT-101 demonstrated exceptional preclinical efficacy in in vivo breast and colorectal cancer models. The candidate compound features a broad therapeutic window and pharmacokinetic properties suitable for daily oral administration as a first-in-class agent, with its intellectual property exclusively licensed to TNA Therapeutics Inc. To expand the scope of our research, we are actively developing proteolysis-targeting chimeras (PROTACs) designed to degrade BCL3.

Funder acknowledgement: Cancer Research Wales

Theme 1, Abstract 9

Abstract Contents

Heparin-derived nanocarriers as a precision medicine drug for therapeutic reprogramming of glioblastoma phenotypic states

Vadim Le Joncour1 , Austin D. Evans2 , Oommen P. Oommen3

1. Translational Cancer Medicine Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.

2. Bioengineering and Nanomedicine Lab, Faculty of Medicine and Health Technology, Tampere University, Korkeakoulunkatu 3, 33720 Tampere, Finland.

3. School of Pharmacy and Pharmaceutical Sciences, Cardiff University, King Edward VII Avenue, Cardiff CF10 3NB, United Kingdom.

Among primary malignant brain tumours, glioblastoma (GB) has the highest incidence and worst prognosis due to infiltrative growth and poor response to current therapy (including surgery, chemotherapy, and radiation). This resistance is largely attributed to the immunosuppressive tumour microenvironment and dynamic phenotypic switching of GB cells, which enables them to adopt drug-resistant mesenchymal-like characteristics that survive therapeutic intervention. We have discovered a novel precision medicine drug employing heparin-based nanoparticles (HP-NPs) designed to cross the blood-brain barrier and target mesenchymal-like glioma stem cells (MES GSCs). The HP-NPs were designed by conjugating fluorescein molecules to the heparin backbone, facilitating self-assembly into 140 nm nanoparticles. We encapsulated doxorubicin (DOX) within HP-NPs (HP-DOX-NPs) to enhance the therapeutic efficacy of the nanocarrier. Encapsulation of DOX reduced drug-mediated complement and coagulation cascade and enhanced hemocompatibility in human whole blood. In vitro, HP-NPs showed efficient cellular uptake across various patient-derived GB cell lines with varying EGFR expression levels. In vivo administration of HP-NPs and HPDOX-NPs in patient-derived xenograft (PDX) models revealed that HP-NPs alone were more effective in suppressing GB progression than their DOX-loaded counterpart. We discovered that HP-NPs homed to the mesenchymal-like glioma stem cells (MES GSCs) expressing heparin-binding epidermal growth factor (HBEGF). HP-NPs targeting MES-like GSCs and downregulating HBEGF lead to differentiation of these drug-resistant cells to more vulnerable astrocyte (AC)-like cells, and oligodendrocyte precursor cell (OPC)-like phenotypic states inducing tumour suppression. Thus, HP-NPs as a promising precision medicine platform to combat GB recurrence and improve patient outcomes by reprogramming GB into treatment-sensitive phenotypes.

Funder acknowledgement: NA

Theme 1, Abstract 10

Abstract Contents

New Wine in Old Bottles - The Therapeutic Promise of the PARP Inhibitor Rucaparib as an N-WASP Inhibitor for Breast Cancer Metastasis

Rhiannon Yanan Yu1, Q Ping Dou2, Elyas Khan2, Wen G. Jiang1 , Tracey A. Martin1

1. Cardiff University School of Medicine, Cardiff, UK

2. Karmanos Cancer Institute, Wayne State University, Detroit, USA

Background

Rucaparib, a well-known PARP inhibitor, is effective in treating BRCA-mutated cancers. Emerging evidence suggests it may also target pathways linked to oncogenesis and metastasis, particularly those involving NWASP proteins, critical for cell motility and invasiveness. This study explores Rucaparib's potential beyond PARP inhibition by targeting N-WASP proteins, providing a novel strategy to counteract cancer metastasis.

Methods

In vitro assays using breast cancer cell lines (MDA-MB-231 and MCF-7) and an endothelial cell line (HECV) evaluated Rucaparib’s effects on cell proliferation, adhesion, and motility. Techniques included cytotoxicity tests, growth assays, Electric Cell-substrate Impedance Sensing (ECIS), wound scratch assays, immunofluorescence, qPCR, and western blotting. Protein docking studies were conducted using computational modelling.

Results

The impact of Rucaparib on cellular dynamics was profound across the studied cell lines. Growth assays showed a statistically significant decrease in cell growth (P=0.0054, P=0.0034, P<0.0001). Rucaparib effectively impaired the ability of cancer cells to adhere and migrate (P<0.0001, P=0.0214, P=0.0003). Rucaparib markedly decreased the RNA and protein levels of N-WASP (P=0.0019, P<0.0001, P<0.0001), indicating a potent inhibitory effect on this metastasis-related protein. These results highlight the potential to disrupt mechanisms underlying metastatic progression, especially N-WASP. Finally, compound docking revealed that Rucaparib had an excellent binding profile with multiple amino acids of key domains of N-WASP protein.

Conclusion

This study identifies Rucaparib as a dual-action therapeutic, effectively targeting both PARP and N-WASP proteins. Its inhibitory effects on proliferation, adhesion, and migration highlight its potential to manage metastatic breast cancer and warrant further clinical investigation.

Funder acknowledgement: NA

Theme 1, Abstract 11

Abstract Contents

Utilizing biological experimental data and molecular dynamics for the classification of mutational hotspots through machine learning

1

James G. Davies1 , Georgina E. Menzies

1. School of Biosciences, Cardiff University

Somatic mutations in the TP53 tumour suppressor gene are implicated in roughly 50% of human cancers, representing the most frequent genetic alterations across lung cancer subtypes. In smoking-related lung cancers, characteristic mutations at hotspot codons such as 157, 158, 245, 248, 273, and 282 have been associated with DNA adducts formed by carcinogens in tobacco smoke, notably benzo[a]pyrene (B[a]P). While B[a]P can bind to numerous genomic sites, only a subset of these adducts drive carcinogenesis, suggesting that the efficiency of DNA repair mechanisms plays a pivotal role in modulating cancer risk. Interestingly, DNA repair efficiency is strongly influenced by local DNA base context, highlighting the role of DNA topology in shaping chemical toxicity. To investigate this, we combined molecular dynamics simulations with machine learning to systematically evaluate the structural distortions induced by BPDE-guanine adducts across various gene contexts. Employing a random forest classifier alongside feature selection, we identified critical structural features that differentiate damage sites with varying repair efficiencies. Our model, trained on helical parameters derived from TP53 hotspot and non-hotspot sites, was then applied to previously unseen structural data from simulations of TP53, cII, and lacZ DNA sequences. This integrated approach provides valuable insights into how DNA topology may influence repair processes, offering a deeper understanding of the molecular mechanisms driving mutagenesis and cancer susceptibility. This work has been previously published in: https://doi.org/10.1093/bioadv/vbae125

Funder acknowledgement: Cardiff University

Theme 1, Abstract 12

Glioblastoma-astrocyte interactions drive tumour progression

Ayesha Begum1, Suresh Kaushik1, Mathew Clement2 , Florian A Siebzehnrubl1

1. European Cancer Stem Cell Research Institute, Cardiff University School of Biosciences

2. Division of Infection and Immunity, Cardiff University School of Medicine

Abstract Contents

Glioblastoma (GBM) is the most frequent and most lethal type of brain cancer in adults, with poor survival rates of 15-20 months with therapy. GBM tumour heterogeneity and therapy resistance are key factors affecting poor survival, and crosstalk between GBM and host cells in the tumour microenvironment (TME) promotes GBM progression, heterogeneity, and therapy resistance. We have previously shown that astroglia can positively or negatively affect brain tumour invasion into the surrounding parenchyma, depending on the status of astroglial reactivity. Here, we investigate cell-cell interactions between GBM and host astrocytes in patientderived orthotopic xenografts and syngeneic in vivo models. We find that GBM-astrocyte crosstalk contributes to the expression of the cell-plasticity associated transcription factor, Zeb1, both in GBM and in host astrocytes. Genetic deletion of Zeb1 in murine astrocytes restricts tumour invasion in vivo and significantly improves animal survival. Using single cell transcriptional profiling, we identify ligand-receptor candidates that mediate GBM-astrocyte crosstalk, and which may constitute therapeutic targets for reprogramming the host TME to reduce GBM progression. Our findings demonstrate that host astrocytes in the TME are powerful regulators of glioblastoma growth and that reprogramming astrocytes can block brain tumour progression.

Funder acknowledgement: FAS is funded by MRC grant MR/X018318/1.

Theme 1, Abstract 13

Pharmacological Inhibition of cFLIP Targets Breast Cancer Stem Cells

Rhiannon French1, Olivia Hayward2, Andreia Ribeiro da Silva2, Timothy Robinson3 , Richard Clarkson2

1. University of Oxford, Sir William Dunn School of Pathology

2. European Cancer Stem Cell Research Institute, Cardiff University School of Biosciences

3. Bristol Medical School (PHS), University of Bristol

Abstract Contents

Advances in breast cancer diagnosis and treatment over the past decades have had significant impact on patient survival, however major challenges remain such as drug resistance and tumour recurrence. Increasing evidence implicates a small subpopulation of cells within the tumour, with the ability to self-renew and differentiate, termed breast cancer stem cells (bCSC), which enable tumours to evade conventional therapies, and promote more aggressive tumours. Therefore targeting bCSCs poses an attractive therapeutic approach to combat cancer. Previous studies have shown the death receptor apoptosis regulator, Cellular FLICE-Like Inhibitory Protein (cFLIP), can protect bCSCs from the cytotoxic chemotherapy effects in vitro. Utilising both a functional in vitro assay and a surrogate marker of CSCs, ALDH, we have shown some chemotherapies such a paclitaxel, whilst successfully decrease tumour burden, also increase bCSC activity in cell lines, and promote tumour recurrence and metastasis in vivo. We have used a novel compound targeted against cFLIP (OH14) in combination with chemotherapy treatment and investigated the impact on bCSC in vitro and in vivo. Here we show that targeted cFLIP inhibition prevents the activation of bCSCs following chemotherapy in vitro and promotes tumour free survival after chemotherapy in models of breast cancer in vivo. These findings provide a proof-of-concept for a novel pharmacological intervention to improve long term survival of breast cancer patients receiving chemotherapy.

Funder acknowledgement: Breast Cancer Now

Theme 1, Abstract 14

Investigating BCL3 as a therapeutic target to treat prostate cancer

Abstract Contents

Tabitha Cunliffe1, Marcos Quintela-Vazquez1, Daniel J. Turnham1, Boris Shorning1, Luke Piggott2, Robert Jones3, Andrea Brancale4 , Andrew Westwell5, Richard W.E. Clarkson1 , Helen B. Pearson1

1. ECSCRI, School of Biosciences, Cardiff University.

2. TNA Therapeutics, USA.

3. ECMC Cardiff, University Hospital Wales, Cardiff University.

4. University of Chemistry and Technology, Prague.

5. School of Pharmacy, Cardiff University.

Metastatic prostate cancer (mPC) remains the leading cause of mortality among patients with prostate cancer, primarily due to its resistance to conventional treatments such as androgen/AR-targeted therapy (ARTT). The oncogenic BCL3-NF-κB signalling pathway is frequently upregulated in advanced PC, including ARTT-resistant disease, thus presenting a novel therapeutic target that is urgently needed to aid patient care. Previously, we have developed a novel range of small molecule BCL3 inhibitors (BCL3i), with the lead compound TNAT-101, that are efficacious against breast and colorectal cancers, and can suppress NF-κB signalling without the tolerability issues associated with current NF-κB inhibitors. Our findings demonstrate that BCL3 is not essential for normal prostate homeostasis in-vivo, and BCL-NF-κB signalling positively correlates with progression rates in PC GEMMs, suggesting BCL3 presents an attractive therapeutic target. TNAT-101 significantly reduced the tumour burden in two castration-resistant mPC PDX models, CUPC01 and PC2400. Furthermore, TNAT-101 decreased proliferation and increased apoptosis in PTEN-deficient HRLPC GEMMs exvivo. Collectively, these findings establish BCL3 facilitates prostate cancer growth and highlight BCL3targeted therapy as a novel therapeutic approach for advanced prostate cancer. Ongoing investigations are underway to explore the functional role of BCL3 in prostate tumorigenesis and ARTT resistance, aiming to determine the stages of disease where TNAT-101 treatment would be the most effective with the ultimate goal of improving survival outcomes and patient care.

Funder acknowledgement: NA

Theme 1, Abstract 15

Pharmacological targeting of Bcl3 improves outcomes in models of colorectal cancer

Hannah Smith1, Huw Morgan1, Adam Higgins1, Cleo Bonnet1, Katie Stott1 , Gillian Seaton1, Richard Clarkson1

Abstract Contents

1. European Cancer Stem Cell Research Institute Cardiff University School of Biosciences Maindy Road Cardiff

Despite major advances in detection, diagnoses and treatment strategies, cancer remains a leading cause of mortality worldwide, with an increasing incidence throughout the population. This increased incidence demands more targeted and effective treatments, provoking a need for a greater understanding of prospective target molecules and therapeutic developments. B-cell lymphoma 3-encoded protein (Bcl3) is a proto-oncogene that modulates cancer-related cell-signalling pathways, including NF-κB and Wnt. Bcl3 is overexpressed in a variety of cancers and exhibits widespread cancer-promoting actions, yet its inhibition is well tolerated, highlighting it as an attractive therapeutic target. We have developed novel Bcl3 inhibitors designed to prevent interactions between Bcl3 and the NF-κB pathway. While our previous studies have shown tumour-efficacy of these inhibitors in models of metastatic breast cancer, we had yet to determine their effects in other cancer types, such as colorectal cancers (CRC), where Wnt signalling is key. Here we show that our lead Bcl3 inhibitor, CB1, exhibited anti-tumour properties in both rectal and colonic cancers, including mutant KRas subtypes. Thus, daily administration of oral CB1 exhibited tumour efficacy in xenograft models of CRC, including regression of mutant KRas SW480 tumours, and potent suppression of metastatic seeding of HCT116 transplants. Furthermore, CB1 significantly reduced organoid and cancer stem cell (CSC) viability within treatment-refractory rectal cancers in vitro. These data confirm that pharmacological targeting of Bcl3 is a promising avenue of investigation for treatment resistant CRCs, targeting those tumour cells responsible for chemotherapeutic resistance and disease relapse.

Funder acknowledgement: This work was in part supported by TNA Therapeutics UK, the UKRI's Medical Research Council (MRC) and the Wellcome Trust

Theme 1, Abstract 16

From healthy pancreas to tumours: identifying the cancer initiating cells

Beatriz Salvador1, Daniel Ruiz-Palacios2, Justo P Castano2, Jen Morton3, Owen Sansom3 , Catherine Hogan1

1. ECSCRI, Cardiff University

2. IMIBIC, Cordoba University

3. CRUK Scotland Institute, Scotland

Abstract Contents

Pancreatic cancer is among the most aggressive cancers with a very poor survival rate. New early detection strategies are urgently needed to improve patient outcome. We showed that KRas mutant cells in adult pancreas can overcome tissue homeostasis mechanisms, remain in the tissue, and initiate Pancreatic Intraepithelial Neoplasias (PanINs). We hypothesise that a subpopulation of KRas mutant cells, never eliminated during tissue homeostasis, develop stem-like properties, and drive PanIN development and progression to pancreatic tumours. By using the KC (Pdx-1CreER;KRasG12D/+;Rosa26LSL-RFP) mouse model and caerulein treatment to induce chronic pancreatitis, we established a model that represents different stages of pancreatic cancer initiation including acinar to ductal metaplasia, low grade PanINs (LG-PanINs), high grade PanINs (HG-PanINs) and early tumours. We studied the transcriptome of single cells at these four timepoints and identified the subset of cells with more stem-like and cancer stem cell properties present in all timepoints. These cells interestingly overexpressed Sca-1 and Nupr1 genes, both already described as important players in pancreatic cancer. Using both protein markers, Sca-1 and Nupr1, we identified cancer initiating cells present in LG- and HG-PanINs and early tumours. Using LG- and HG-PanIN organoids we confirmed that Nupr1 inhibition impairs organoid growth. We also found that Sca-1high PanIN cells have a higher sphere formation potential compared to Sca-1 negative cells. Future work will address the ability and/or requirement of Sca-1high/Nupr1high to initiate PanINs and tumours cells and their ability to initiate PanINs and tumours. Finally, we will validate the presence of these cells in human tissues.

Funder acknowledgement: Pancreatic Cancer UK

Theme 1, Abstract 17

Abstract Contents

Concentrative Nucleoside Transporter 1 (hCNT1)/SLC28A1 and Equilibrative Nucleoside Transporter 1 (hENT1)/SLC29A1 in human colon cancer, the clinical and therapeutic considerations

Matthew McKenna1 , Amber Li1 , Lin Ye1 , Tracey Martin1 , Wengou Jiang1 , Rachel

Hargest

1

1. Cardiff University

Colorectal cancer (CRC) remains a global health challenge despite advancements in screening, diagnosis, and treatment. While surgical resection offers the only curative option, patients diagnosed beyond stage I typically require adjuvant therapies such as chemotherapy or radiotherapy. Most screen-detected cases are identified at stages I–II, whereas non-screen-detected cases are often diagnosed at stages III–IV (Cardoso et al., 2022), emphasising the need for effective adjuvant treatment strategies. This study explores the clinical significance of the nucleoside transporter hENT1 in CRC and its potential as a predictive biomarker for therapeutic response. Preliminary analysis from a Cardiff colon cancer cohort revealed that high hENT1 expression in primary CRC was associated with poor overall survival, disease-free survival, and distant metastasis-free survival. Notably, patients with high hENT1 expression who received nucleoside analogues demonstrated improved outcomes, suggesting a potential therapeutic role. RNA and proteomic analyses of CRC cell models demonstrated heterogeneous hENT1 expression, enabling the development of knockdown models using lentiviral shRNA. These models, combined with drug sensitivity assays, will be used to evaluate the therapeutic potential of targeting hENT1. It is hypothesised that hENT1 expression is a key prognostic and therapeutic indicator for commonly used drugs such as fluorouracil (5-FU), with significant implications for personalised treatment strategies in CRC. These findings may support the development of hENT1-targeted therapies to improve patient outcomes.

Funder acknowledgement: Royal College of Surgeons England

Theme 1, Abstract 18

Development

Abstract Contents

and Validation of a Novel Multi-Functional Iron Oxide Nanoparticle for the Targeted Induction of Ferroptosis in Cancer

Darius McPhail1, James Cronin2, Rebecca Wurelly2 , Rhiannon Beadman2, Joel Crane3, Mark Davies1, Debabrata Tripathy4, Richard Yuxiong Su4, Andrew Tee1, Juan Mareque-Rivas3

1. School of Medicine, Cardiff University

2. Swansea University Medical School, Swansea University

3. Department of Chemistry, Swansea University

4. Division of Oral and Maxillofacial Surgery, University of Hong Kong

Ferroptosis is a recently discovered form of iron-driven cell death, wherein intracellular ferrous iron results in lipid peroxidation (LPO) and oxidative stress. Due to the inherent iron-dependency of cancer, ferroptosis may be an exploitable mode of cell death in the treatment of cancers which are resistant to conventional chemotherapeutics. We have developed a novel iron oxide nanoparticle (IONP) for the targeted induction of ferroptosis in cancer. IONPs were coated in FDA-approved PEGylated phospholipids and MC3-DLin-DMA. MC3DLin-DMA (used in clinically-approved lipid nanoparticles (LNPs)) provides two polyunsaturated fatty acid (PUFA) chains to initiate ferroptosis. These PUFA-rich, PEGylated, phospholipid-stabilized Fe3O4-filled micelles were characterised by size, shape, and charge. Uniquely, the pro-ferroptotic activity of this IONP is initiated by spontaneous homolysis of hydroperoxides and the reaction of H2O2 with Fe(II) ions within the micelles. The IONP self-generates hydroxyl and alkoxyl radicals that ultimately cause LPO in cells. The efficacy of IONPs in inducing ferroptosis was measured in vitro by viability and LPO assays. The potency of IONPs could be enhanced with the use of RNA interference for a key ferroptosis defence gene (AIFM2). In vivo studies demonstrated that IONPs administered by subcutaneous injection or transdermal delivery using fastdissolving microneedle patches provide high efficacy in the reduction of tumour volume at low doses. This study has developed and validated an effective and innovative cancer drug which uses a multi-functional approach to induce ferroptosis. It is intended for this drug to progress to further pre-clinical trials and be evaluated in combination with pro-ferroptotic drugs.

Funder acknowledgement: NA

Theme 1, Abstract 19

Abstract Contents

Impact of Brain-Derived Neurotrophic Factor (BDNF) on Tight Junction (TJ) Proteins and Cell Adhesion and Migration in Breast Cancer: Implications for Brain Metastasis

Milad Eshmela1, Wen G. Jiang1, Lin Ye1, Tracey A. Martin1

1.

CCMRC, Cardiff University School of Medicine, Cardiff, Wales, UK

Background

Brain-Derived Neurotrophic Factor (BDNF) plays a significant role in the modulation of tight junction-(TJ)proteins and influences cell adhesion and migration, which are essential for both cancer metastasis and blood-brain-barrier (BBB) integrity. This study investigates the effects of BDNF on the expression of TJ proteins and the functional consequences on cell adhesion and migration in breast cancer cells and brain endothelial cells.

Methods

Following treatment with BDNF, changes in the expression of TJ proteins including claudins, occludin, ZOs, JAMs, MAGIs and Nectins were assessed using quantitative PCR (qPCR) at different time points (30minutes, 60minutes, 2hours, 4hours, and 24hours) with a baseline control (0-time point) in both MDA-MB-231 (breast) and HMECD3 (endothelial) cell lines. BDNF knockdown models were created using anti-BDNF siRNA to assess the functional consequences of BDNF signalling on cell adhesion and migration using Electric Cell-Substrate Impedance Sensing (ECIS).

Results

qPCR results indicated dynamic alterations in the expression of multiple TJ proteins, suggesting a regulatory role for BDNF in the maintenance of cell-cell adhesion and barrier integrity in both cell types. Additionally, BDNF Knockdown resulted in a significant decrease in cell adhesion and migration, highlighting the importance of BDNF in promoting the migratory behaviour of cancer cells and in maintaining BBB integrity.

Conclusion

These findings suggest that BDNF is a key regulator of cell adhesion, migration, and TJ proteins expression, implicating its role in cancer metastasis. Targeting BDNF could provide a novel therapeutic strategy to inhibit cancer cell migration and stabilize BBB integrity, preventing brain metastasis from breast cancer.

Funder acknowledgement: Ministry of Higher Education and Scientific Research-Libya

Theme 1, Abstract 20

Abstract Contents

Artemisinin Modulates Tight Junction Integrity in Breast Cancer Brain Metastasis Through the Wnt/βCatenin Pathway

Wenxiao Ji1, Wen G. Jiang1, Tracey

A. Martin

1

1. Cardiff China Medical Research Collaborative

Background

The Wnt/β-catenin (CTNNB1) signalling pathway plays a critical role in breast cancer progression and metastasis, closely linked to the function of tight junction proteins such as Claudin-8 (CLDN8). Dysregulation of CLDN8 disrupts the integrity of the blood-brain barrier (BBB) and enhances cancer cell invasiveness. Artemisinin, a natural compound, has demonstrated potential in modulating CLDN8 expression and influencing the Wnt signalling pathway. This study investigates the effects of artemisinin on CLDN8, CTNNB1, and Wnt signalling in the context of breast cancer brain metastasis.

Methods

CLDN8 expression was silenced using siRNA in brain endothelial cells (h CMEC/D3) and breast cancer cell lines (MDA-MB-231, SKBR3, MCF-7), followed by treatment with 10 μM artemisinin. Western blot, immunofluorescence, and co-immunoprecipitation were used to analyse the expression, localization, and interactions of CLDN8, CTNNB1, and glycogen synthase kinase 3 beta (GSK3β). Functional assays, including trans endothelial electrical resistance (TEER), cell invasion assays, and Wnt signalling activity evaluation, were performed to assess the effects of artemisinin on cell behaviour and signalling pathways.

Results

Artemisinin significantly reduced CLDN8 expression and enhanced GSK3β activity, as evidenced by increased phosphorylation at Tyr216 and dephosphorylation at Ser9. Activated GSK3β promoted CTNNB1 phosphorylation at Thr41/Ser45, leading to its degradation and inhibition of Wnt signalling activity. Functional assays demonstrated that artemisinin disrupted BBB integrity (decreased TEER values) but inhibited breast cancer cell migration and invasion, suggesting a reduction in metastatic potential mediated through Wnt pathway regulation.

Conclusion

Artemisinin modulates CLDN8 and CTNNB1 expression and function via the Wnt/β-catenin signalling pathway, demonstrating dual effects of enhancing drug delivery capacity and inhibiting breast cancer brain metastasis. This study provides molecular insights into the potential therapeutic application of artemisinin in treating breast cancer brain metastases.

Funder acknowledgement: NA

Theme 1, Abstract 21

Abstract Contents

A Molecular Dynamics Study of Differential Base Excision Repair in Cancer Associated DNA loci by OGG1 Machinery.

Lily James-Knight1, James Davies1, Georgina Menzies1

1. School of Biosciences, Cardiff University, Wales

DNA repair is essential for preventing oncogenic events by correcting DNA damage. One disease- associated lesion, caused by reactive oxygen species (ROS), is 8-oxo-guanine (8-oxoG). Although 8-oxoG is not inherently mutagenic, unresolved lesions can lead to mismatched DNA replication and mutagenesis. Base Excision Repair (BER), the pathway responsible for resolving 8-oxoG, is often sequence-dependent, meaning repair efficiency relies on the local DNA environment. The BER enzyme OGG1, a DNA glycosylase, plays a central role in recognising and excising 8-oxoG lesions. OGG1's activity is hypothesised to be influenced by both its structural conformation and the surrounding DNA sequence. In this study we have created a computational model to investigate mutational hotspots in cancer-associated genes, focusing on the interplay between DNA sequence variability and BER efficiency. We have examined how 8-oxoG-induced distortions impact DNA helices, particularly at KRAS codons K12 (poorly repaired) and K14 (well-repaired). Further to this, using molecular dynamics (MD), stability analyses, and binding energy studies, we are exploring the effects of disease-linked OGG1 protein mutants on DNA docking and repair efficiency. This research seeks to uncover key factors critical for DNA repair in cancer-relevant contexts, enhancing our understanding of BER mechanisms at the molecular level.

Funder acknowledgement: Cardiff University

Theme 1, Abstract 22

Long-read transcriptomics of alternatively spliced RNA isoforms in pancreatic ductal adenocarcinomas.

Garan

Jones1, Harsh Bhatt1, Duncan Baird1

1. Division of Cancer and Genetics, Cardiff University

Introduction

Abstract Contents

Pancreatic cancers remain incredibly challenging to treat, with a complex tumour microenvironment and a paucity of mechanistic targets for therapeutic application.

Previous work on pancreatic ductal adenocarcinomas (PDAC) (PMID: 33589694) has shown that dysregulation of transcription and the presence of alternate isoforms may be associated with the development of these tumours. This may provide a druggable target for antisense oligonucleotides or small molecule inhibitors. With emerging technologies now available, we can utilise

Oxford Nanopore Technologies’ (ONT) long-read sequencing (LRS) of RNA transcripts, to discover intact novel isoforms.

Aims

To study intact novel transcript isoforms within PDACs, in the context of non-diseased human pancreas, using LRS transcriptomics.

Methods

Six matched tumour / control pairs from patients with pancreatic ductal adenocarcinoma were obtained from the Wales Cancer Biobank. Following ethics approval, the samples were sequenced using ONT LRS cDNA transcriptomic sequencing via DeepSeq (Univ. of Nottingham). Subsequent data analysis by Epi2Me transcriptomic workflow produced novel transcript isoforms, as well as potential gene fusion products.

Results

Novel transcript isoforms and gene fusion products related to the PDAC tumour samples, but not present in matched controls, will be presented. Pathway analysis will be demonstrated to highlight potential mechanisms related to cancer progression and development. The resolution of intact transcript reads will provide confirmation of alternatively spliced isoform transcripts.

Funder acknowledgement: Advanced Therapies Wales

Theme 1, Abstract 23

Abstract Contents

Exploring the mechanism and predictability of KRASG12D cell elimination mechanisms in the adult pancreas.

Non Williams1, Beatriz Salvador-Barbero1, Maria Secrier2, Catherine Hogan1

1. European Cancer Stem Cell Research Institute, Cardiff University

2. UCL Genetics Institute, University College London

Epithelial tissues are constantly subjected to mutational challenges and have evolved homeostatic defence mechanisms to identify and eliminate aberrant cells. Mutant cells must override this competitive elimination to survive and promote cancer development. Pancreatic cancer primarily arises from sporadic KRAS mutations, and our previous work showed that KRASG12D cells compete with their normal neighbours for space and survival, with the majority being actively eliminated from the tissue. The pancreas is a slow-proliferating epithelial tissue, reliant on cellular plasticity and reprogramming for tissue repair. We recently showed that some KRASG12D cells can escape elimination and are retained in the tissue by adopting a plastic, dormant state, driven by Wnt5a signalling. We aim to further explore the contribution of cellular plasticity to cell elimination in vivo, hypothesizing that non-eliminated KRASG12D cells constitute a progenitor-like population with an increased capacity to reprogram into a dormant state under cellular stress. Using spatial transcriptomics, we will identify molecular mechanisms underlying cell elimination, focusing on Wnt signalling, cell dormancy and stemness, cellular stress and injury, and cell-cell interaction signals. Additionally, we will investigate the predictability of KRASG12D cell elimination, based on tissue location and local cellular environments. Unravelling the molecular and spatial dynamics of cell elimination will provide crucial insights into the mechanisms of pancreatic cancer initiation, with potential implications for improving cancer prevention, detection, and treatment strategies.

Funder acknowledgement: NA

Theme 1, Abstract 24

Abstract Contents

Investigating the predictive value of cancer-associated fibroblasts (CAFs) in prostate cancer

Anna Richards1 , Tegen Hooper1, Jasmine Owen1, Leah Officer-Jones2, Silvia Cusumano2, Michelle Somerville3, Lisa Spary4, Awen Gallimore3, John Le Quesne2, Helen Pearson1

1. The European Cancer Stem Cell Research Institute, School of Biosciences, Cardiff University

2. Cancer Research UK Scotland Institute (CRUK SI), Glasgow

3. School of Medicine, Cardiff University

4. Wales Cancer Bank, University Hospital Wales

As the second-leading cause of cancer-related deaths in men globally, 1-in-8 men are predicted to be diagnosed with Prostate Cancer (PCa) in their lifetime. Current standard-of-care therapies, including hormonebased and chemotherapeutic strategies, exhibit limited efficacy, underscoring the urgent need for novel therapeutic approaches and a deeper molecular understanding this lethal disease. Cancer-associated fibroblasts (CAFs) are regulators of androgen/PI3K signalling and remodel the tumour microenvironment (TME) to drive tumour progression and drug resistance. However, the predictive value of CAF subpopulations, their role in PCa progression, and their influence on therapeutic sensitivity remain poorly understood. We hypothesise that prostate CAF subpopulations hold predictive value and mediate therapeutic resistance, presenting a potential therapeutic target. To date, we have developed high-plex imaging approaches, including a custom 40-plex Phenocycler immunofluorescence panel to characterise CAF subpopulations in a novel tissue microarray (TMA) containing prostatectomy specimens (plus matched normal tissue) from patients that either relapsed within or after 5-years post-prostatectomy. Additionally, we have investigated the functional role of PI3K/AKT signalling in both established and primary prostate CAF/normal fibroblast cell lines in vitro. Our findings have revealed that AKT inhibition does not affect normal fibroblast viability in vitro but drives stromal expansion in vivo, suggesting CAF-mediated events modulate treatment response. Ongoing work is characterising CAF subpopulations/location/abundance to determine whether a phenotypic switch impacts tumour growth and therapy outcomes. Ultimately, our research aims to uncover predictive CAF biomarkers and therapeutic targets to improve patient outcomes, addressing the critical need for novel strategies in PCa.

Funder acknowledgement: Wales Cancer Research Centre/Health Care Research Wales and Cancer Research UK

Theme 1, Abstract 25

Abstract Contents

A systematic approach to identify charged repurposed therapeutics for affinity-based local drug delivery systems for glioblastoma treatment.

Sabarni Sarker1,2, Christodoulos Theodoulou1, Benjamin Newland1

1. School of Pharmacy and Pharmaceutical Sciences, Cardiff University

2. Department of Pharmacy, Jagannath University, Dhaka

Background

Treatment of glioblastoma (GBM) presents significant challenges due to its high degree of heterogeneity and poor prognosis. Recurrence of the malignancy is frequent even after standard treatment, including surgery, radiotherapy, and chemotherapy with temozolomide. Drug repurposing offers a cost-effective strategy to identify new treatments, while affinity-based local delivery systems could provide controlled release of therapeutics in the tumor resection cavity.

Objective

This study aims to systematically search charged repurposed therapeutics chemically suitable for affinitybased local delivery in the GBM resection cavity.

Methods

To screen for chemical suitability and anticancer efficacy 969 neurology and anti-infective therapeutics were selected from Broad Institute Drug Repurposing Hub. Charge, lipophilicity, solubility at pH 7.4 were calculated by Chemicalize. Systematic search for the anticancer efficacy of the charged compounds were carried out from the following database: PubMed, Scopus, Sci-Finder and ClinicalTrial.gov.

Results

Among the 969 compounds, 584 were identified as charged at physiological pH. Of these, 145 neurology and 87 anti-infective agents exhibited anticancer properties. Notably, 90 neurological candidates showed activity against at least one type of brain neoplasm. Few compounds, such as chlorpromazine and chloroquine, were investigated in clinical settings, while most were assessed in in vitro viability studies.

Conclusion

This study identified few potential repurposed GBM therapeutics for affinity-based delivery in the tumour resection cavity. Prioritized candidates will undergo further in vitro screening and loading-release studies to predict their affinity-based controlled release patterns in the resection cavity.

Funder acknowledgement: NA

Theme 1, Abstract 26

Abstract Contents

Noninvasive Microstructure Reconstruction for Prostate Cancer Using Diffusion MRI: Phantom Validation and Clinical Potential

Yang Yang

1,2, Adam

Threlfall

1,3,

Leandro Beltrachini

1,2

1. Cardiff University Brain Research Imaging Centre (CUBRIC), Cardiff University

2. School of Physics and Astronomy, Cardiff University

3. School of Computer Science and Informatics, Cardiff University

Characterizing cancerous tissue microstructures is essential for accurate diagnosis and personalized treatment. The Gleason grading system, based on histological analysis, has long been the gold standard for diagnosing prostate cancer. However, invasive biopsies are often costly, painful, and associated with risks such as infection or disease progression. As a less invasive alternative, magnetic resonance imaging (MRI) has been explored, but its limited spatial resolution frequently reduces diagnostic specificity. Diffusion MRI (dMRI) has shown promise by capturing the motion of water molecules, which reflects the underlying microstructural features of tissues. However, conventional dMRI-based approaches often rely on simplified models that fail to fully capture the complexity of tumor tissue architecture. This creates a need for more advanced and robust methodologies. In this work, we present a novel approach inspired by materials science to reconstruct histology-like tissue microstructures from dMRI signals. By leveraging statistical descriptors derived from the measured diffusion data, our method enables "virtual biopsies," offering detailed microstructural insights without the need for invasive procedures. The feasibility of this approach is demonstrated through validation using both simulated datasets and physical phantoms, with reconstructed structures compared against microscopic images. Preliminary results highlight improved accuracy in capturing cell-like features and a greater resilience to model assumptions. This study represents a significant step toward a robust virtual histology pipeline that could enhance cancer diagnosis and treatment planning. By enabling more personalized and less invasive diagnostic strategies, this approach has the potential to improve patient outcomes in oncology.

Funder acknowledgement: NA

Theme 1, Abstract 27

Abstract Contents

Identification of CENPB as a Novel Candidate Therapeutic Targets in Acute Myeloid Leukaemia using Proteomic

Analysis of Patient Material

Halawi, MA1,2, Smith, D3, Alanazi, MO1,4, Rizzo, S1, Hughes, OM1, Alruwaili, AM1,6 , Knapper, S1, Tonks, A1, Darley, RL1

1. Department of Haematology, Division of Cancer and Genetics, School of Medicine, Cardiff University, Cardiff, UK

2. College of Pharmacy, Jazan University, Jazan, Saudi Arabia

3. Cancer Research UK Manchester Institute, University of Manchester, Manchester, UK

4. College of Applied Medical Science, Shaqra University, Riyadh, Saudi Arabia

5. Department of Haematology, Division of Cancer and Genetics, School of Medicine, Cardiff University, Cardiff, UK

6. Medical Laboratory Technology Department, College of Applied Medical Sciences, Northern Border University, Arar, Saudi Arabia * Presenting Author

Despite advances in treatment, acute myeloid leukaemia (AML) outcomes remain poor, particularly for older individuals. Targeted therapies are the best chance to improve survival. Here, I identify abnormally expressed proteins in AML using mass spectrometry. The proteomic profile of AML patient samples (n=91) was compared to normal haemopoietic cells (n=5). Out of 4,888 detected proteins, 1,406 proteins differed between AML and normal cells (p <0.05). Amongst these overexpressed proteins, I identified centromere protein B (CENP-B). This protein plays a role in chromosomes segregation and was significantly upregulated in (83%) of AML samples compared to normal controls (20%), with an average 2-fold overexpression (p< 0.0000005). Western blot analysis of 20 AML samples and 3 normal control samples confirmed upregulation in AML observed in mass spectrometry data. A western blot survey of six AML cell lines also showed CENP-B expression. To establish its role in AML proliferation and survival, I knocked-down CENP-B for three cell lines using two shRNA constructs. CENP-B expression was reduced by >80% compared to control. This led to decreased proliferation (50%-67%, p <0.0001), while viability remained unaffected. Conversely, while overexpression of CENP-B in AML cell lines (2-fold) was tolerated, overexpression of CENP-B in primary CD34+ cells markedly reduced viability inducing a >3-fold increase in the frequency of apoptotic cells suggesting that constitutive expression of CENP-B throughout the cell cycle is lethal in normal cells. In summary, I identified >1400 mis-regulated proteins in AML and have shown that the overexpression of the centromere protein CENP-B is important to maintain optimal proliferation in AML cells.

Funder acknowledgement: Jazan University, Jazan, Saudi Arabia

Theme 1, Abstract 28

TRPML1, a novel drug target for broad use in Triple Negative Breast Cancer treatment

Bethany

Tattersdill1

1. Cardiff University

Abstract Contents

Triple negative breast cancer (TNBC) accounts for 15-20% of all breast cancer patients, with a 5-year survival rate of 60%. Despite there being many sub-types which respond differently to therapeutics, from a clinical perspective TNBC patients are largely treated irrespective of their tumour profile. This has led to low treatment effectivity, high relapse rate and low survival probability, prompting researchers to explore more downstream targets. Many recent studies have elucidated TRPML1, a lysosomal Ca2+ channel, as a compelling target due to its role in regulating lysosomal function, autophagy, and cellular homeostasis - key processes in aggressive cancer progression and survival. We show across a panel of cell lines that treatment with the commercial TRPML1 inhibitor, ML-SI1, for 48h significantly inhibits TNBC cell proliferation, migration, invasion and cancer stemness by at least 50%, all key mechanisms in tumour development and progression. We also demonstrate via immunofluorescence intracellular trafficking pathways by which this occurs, including impairment of endosomal and autophagic processes which impacts to cellular metabolic turnover. Further to this we show mitochondrial function is impaired and suggest this as a potential anti-cancer mechanism. Most importantly, we show that these phenotypes are consistent across all TNBC sub-types, further evidence that TRPML1 is a good candidate for therapeutic target and that it can be effective for broad administration for TNBC patients.

Funder acknowledgement: NA

Theme 1, Abstract 29

Abstract Contents

Adaptive therapy treatment: Utilising the evolutionary dynamics between different tumour cell populations for Cancer treatment

Liam

Ryall-Friend1, Noemi Picco1, Mark Davies2

1. Faculty of Science and Engineering, Swansea University, 2. Cardiff University

Adaptive therapy uses evolutionary and ecological principles to limit the tumour size to a less harmful level capitalising on the dynamics between different subclones with varying sensitivities to a drug. Adaptive therapy often involves periods of time involving treatment from a drug followed by treatment free intervals. This approach allows patients to have suitably tailored treatment programmes based on how the tumour has previously responded to therapy. Commonly, treatment is monitored after several weeks using invasive tissue biopsies that are unsuitable for frequent use in a clinical setting. Biomarkers such as ctDNA provides clinicians with a minimally invasive method to monitor tumour burden and tumour heterogeneity in real time. These ctDNA levels can provide critical insights to guide clinicians in adapting treatment schedules. In this poster a novel mathematical model consisting of a system of ordinary differential equations is presented that describes the dynamics between 2 subclones interacting with a drug and the associated ctDNA dynamics. This modelling framework serves as a test bed for theoretical investigation, and underscores the potential of ctDNA to inform optimal treatment strategies, enhancing the effectiveness of adaptive therapy.

Funder acknowledgement: EPSRC, Swansea Bay University Health Board

Theme 1, Abstract 30

Incorporating Toxicity Feedback to into Adaptive Cancer Therapy

Mark Davies1, Joel Brown2, Jana Gevertz3, Harsh Jain4, Irina Kareva5, Eduardo Sontag5, Kathleen Wilkie6

1. Department of Cancer and Genetics, Cardiff University

2. Department of Integrated Mathematical Oncology, Moffitt Cancer Center

3. Department of Mathematics and Statistics, The College of New Jersey

4. Department of Mathematics and Statistics, University of Minnesota - Duluth

5. Department of Mathematics, Northeastern University

6. Department of Mathematics, Toronto Metropolitan University

Abstract Contents

Adaptive therapy has emerged as a promising approach to cancer treatment by dynamically adjusting dosing schedules to exploit competitive interactions between drug-sensitive and drug-resistant tumour cell populations. By maintaining a balance between these populations, adaptive therapy aims to delay the emergence of resistance, which is a major limitation of traditional continuous therapy. However, most models of adaptive therapy neglect the impact of treatment-induced toxicity, a critical factor affecting both patient outcomes and treatment feasibility. This study investigates how incorporating toxicity feedback influences the performance of adaptive therapy protocols. Using a mathematical framework that integrates tumour dynamics, pharmacokinetics, and toxicity accumulation, we compare four treatment strategies: continuous therapy; adaptive therapy; continuous therapy with toxicity feedback; adaptive therapy with toxicity feedback Our results demonstrate that incorporating toxicity feedback significantly enhances the time to progression (TTP) by optimizing treatment schedules to balance efficacy and tolerability. This improvement is achieved by leveraging both the competitive dynamics of tumour populations and real-time feedback on patient toxicity levels, ensuring that treatment remains effective while minimizing harm.

Funder acknowledgement: NA

Theme 1, Abstract 31

Abstract Contents

Assessing an αvβ6 integrin selective virus-directed enzyme prodrug therapy (VDEPT) in pre-clinical models of Gastric and Head and Neck cancers

Jaya

L Vangara1,3, Luned M Badder1, Sandeep Berry4, Toby J Phesse2, Mererid Evans1,3, Alan L Parker1

1. School of Medicine, Cardiff University

2. European Cancer Stem Cell Research Institute, Cardiff University

3. Velindre Cancer Centre

4. Department of ENT, University Hospital of Wales

Gastric and Head neck (H&N) cancers have poor outcomes despite recent advances in therapies. One promising therapy is Virus Directed Enzyme Prodrug Therapy (VDEPT) using a targeted virotherapy. Adenovirus 5 (Ad5) has been widely studied for its suitability as a cancer therapeutic. Ad5 naturally binds coxsackie and adenovirus receptor (CAR), blood clotting factor X (FX), and αvβ3/5 integrin, using each major capsid protein (fiber, hexon and penton base), making it non-cancer selective and rapidly sequestrated by healthy tissues, unless modified extensively. To overcome these issues, we engineered Ad5 to remove native tropisms, then incorporated a 20 amino acid, αvβ6 integrin interacting peptide (A20) to generate Ad5NULL-A20. These modifications restrict transduction to αvβ6, which is upregulated in many carcinomas including gastric and H&N cancers, whilst expression is absent or undetectable in normal tissue. We incorporated the suicide gene, FCU1, which encodes a heterobifunctional enzyme, into Ad5NULL-A20. Ad5NULL-A20.FCU1 converts a non-toxic antifungal agent, 5-FC (5-fluorocystine), to active chemotherapy 5-Fluorouracil (5-FU), and metabolite 5-FU monophosphate (MP). We assessed the efficacy of this therapy in a range of concentrations of virotherapy and 5-FC to determine the therapeutic window by calculating IC50 using viability assays in cancer cell lines. We demonstrate αvβ6+ carcinomas are sensitised to 5-FC following transduction with Ad5NULL-A20.FCU1 in a dose-dependent manner, showing VDEPT is effective therapy in preclinical models of these cancers. Our future work will focus on assessing cell viability assay for further gastric and H&N primary isolates and organoids, and correlate with αvβ6 integrin status.

Funder acknowledgement: Wales Cancer Research Centre, Velindre Cancer Centre

Theme 1, Abstract 32

Abstract Contents

Evaluation of PDK1 as a Therapeutic Target in Acute Myeloid Leukaemia: Mitigating ROS-Induced PI3KAKT Activation

Alruwaili AM1,2, Rizzo S1, Shahid Ullah1, Hughes O1, Flores J1, Gough F1, Alanazi MO1,3, Halawi M1,4, Niamh O’Neill1, Knapper S1, Darley RL1 , Tonks A1

1. Department of Haematology, Division of Cancer & Genetics School of Medicine, Cardiff University, Cardiff, CF14 4XN, Wales, UK.

2. Medical Laboratory Technology Department, College of Applied Medical Science, Northern Border University, Arar 91431, Saudi Arabia.

3. College of Applied Medical Science, Shaqra University, Shaqra 15572, Saudia Arabia.

4. College of Pharmacy, Jazan University, Jazan 82913, Saudi Arabia.

The development of treatments that minimise treatment resistance and prevent relapse is a priority in acute myeloid leukaemia (AML). We have previously identified the overproduction of extracellular NOX2-derived reactive oxygen species (ROS) by AML blasts. ROS play an important role, not only in immune defence but also in regulating intracellular signalling and are contributing factors in several cancer models. Uncontrolled AML cell proliferation is promoted by ROS, likely as a consequence of hyperphosphorylation of serine/threonine protein kinases. Here we show how ROS affects the kinome of AML cells. Using the MV4;11 AML cell line (in which NOX-derived ROS is undetectable), I demonstrated that glucose oxidase (GOX) induced ROS, increased proliferation, and elevated the phosphorylation levels of PDK1, mTOR, and Phospho-S6 Ribosomal Protein, indicating activation of the PI3K-AKT pathway. I evaluated the therapeutic effectiveness of PDK1 inhibition using GSK2334470 to antagonise these effects. GSK2334470 treatment successfully normalised phosphorylation patterns, significantly decreasing the phosphorylation of essential downstream signalling proteins associated with cell cycle control and apoptosis suppression. Concomitantly, I observed a significant reduction in cellular proliferation rates and glucose absorption, indicating a normalisation in the metabolic processes of AML crucial for cell growth and survival. These data illustrate the essential function of PDK1 in facilitating ROS-augmented signalling within the PI3K-AKT pathway. The capacity of GSK2334470 to attenuate the pathogenic activation of the PI3K-AKT pathway triggered by ROS in AML cells presents a possible therapeutic approach to inhibit the malignant progression of AML by modifying essential signalling nodes influenced by oxidative stress.

Funder acknowledgement: Northern Border University

Theme 1, Abstract 33

Abstract Contents

Examining the clinical impact of telomere length and dysfunction in squamous cell carcinoma of the head and neck (HNSCC)

Ashley Poon-King1,2, Kevin Norris1,3, Paola Foulkes4, Sandeep Berry5, Mererid Evans1,2, Duncan Baird1,3

1. Department of Cancer and Genetics, School of Medicine, Cardiff University

2. Velindre NHS Trust

3. Telonostix Ltd Biotechnology Services

4. Wales Cancer Biobank, Cardiff University

5. Cardiff and Vale University Health Board

Telomeres are structures that cap the ends of chromosomes, preventing the natural chromosome end from being recognised and processed by the cellular DNA damage response. Telomere dysfunction including telomere fusion events in tumour cells can result in genomic instability that can help facilitate clinical progression, and there is a correlation between shortened telomeres and poor prognosis/response to treatment in several tumour types. Telomere length (TL) also correlates with immune aging and has been shown to shorten following radiotherapy/chemoradiotherapy (RT/CRT) for HNSCC. In this study highthroughput single telomere length analysis (HT-STELA) was applied to DNA extracted from tumour tissue and circulating leukocyte cells taken 5-7 days prior to, and at 1- and 3-months following RT/CRT in patients receiving treatment for HNSCC. Samples have also been screened for presence of telomere fusion events. Data from 67 samples analysed show variation in mTL with evidence of shortened TL. Fusion events were also detected in samples screened. Leucocyte telomere dynamics performed on 4 patients showed evidence of persistent bimodal TL distributions in 3 patients, a transient decrease in mTL 1 month post CRT/RT with recovery at 3 months. This decrease was not seen in the single patient who did not have nodal irradiation. These data reveal evidence of telomere dysfunction in HNSCC. Ongoing work including long-read sequencing of fusion events will help establish the extent to which telomeric mutation impacts the HNSCC genome. Analysis of clinical follow-up data will establish whether telomeric parameters may provide clinically useful prognostic and predictive information in this disease.

Funder acknowledgement: Wales Cancer Research Centre, Velindre Charitable Funds

Theme 1, Abstract 34

Abstract Contents

The Wales Cancer Biobank Digital (WCB Digital) project: An All-Wales approach to integrated sample and genomic data access for the cancer research community.

Liz Merrifield1, Dr. Peter Giles1 , Prof. Richard Clarkson2, Prof. Richard Adams2, Dr. Lisa Spary2, Abigail Macarthur2, Sian Morgan3, Dr. Erik Waskiewicz3, Dr. Sophie Shaw3

1. BioResource Data Accelerator, Wales Gene Park, Cardiff University

2. Wales Cancer Biobank, Cardiff University

3. All Wales Medical Genomics Service

We are excited to announce the WCB Digital project which presents an exciting collaboration of national services, the Genomics Partnership Wales, Wales Cancer Biobank (WCB), the All-Wales Medical Genomics Service (AWMGS) and Cardiff University’s Advanced Research Compute team (ARCCA). This project delivers upon key research components of the Genomics Delivery Plan for Wales and CReSt strategies by establishing a brand new genomic data pathways from the NHS to the cancer research community. WCB Digital will link patient samples with genomic profiles, routine diagnostic results, treatment and outcome datasets for breast, lung, prostate and colorectal cancers, amongst others. This is a unique model in terms of UK and Welsh cancer research.

WCB Digital will enrich WCB’s resource offerings, whilst utilising the broad research consent and ethical approval models currently in operation. To date, project activities have included working closely with the HRA to ensure the adequacy of data classification and transparency information provided to the public, plus steps to establish appropriate technical and information governance safeguards facilitating the flow of sensitive data from the NHS environment, including anonymisation. Extensive work has been undertaken to ensure compliance at all stages, thereby providing appropriate assurances to NHS partners, patients and the public of the onward use of this data.

The WCB Project intend to present a poster and presentation to outline the key steps undertaken to reach this point, and onward plans for the routes to utilise this data as scalable, reproducible analytical pipelines for future cancer research.

Funder acknowledgement: HCRW, GPW, ECMC, Roche

Theme 1, Abstract 35

Abstract Contents

Gleason Grading of Prostate Cancer Tissue using novel DRAQ5&Eosin Fluorescent Labels and AI classification algorithms.

Michail Georgios Papachristos1, David Hywel Thomas2, Finni Akinade3, Anna Wilson4, Emiliano Spezi5, Rachel Errington6, Dimitris Parthimos1

1. School of Medicine, Division of Cancer and Genetics, Cardiff University

2. Consultant Histopathologist, University Hospital of Wales

3. School of Medicine, Cardiff University

4. University of Alabama at Birmingham

5. School of Engineering, Cardiff University

6. Head of School of Medicine, Cardiff University

Background

Diagnosis of Prostate Cancer relies on Gleason Grading (1-5) to quantify cancer progression. Recent developments in this field include novel biomarkers, imaging and analytical techniques developed for prostate tissue characterization.

Aims and Methods

We aim to develop AI algorithms capable of integrating multi-modal biological information to improve prostate cancer grading. We have obtained prostate tissue sample cores from a commercial Tissue Microarray, subsequently annotated by an expert oncologist. A novel labelling technique based on DNA stain DRAQ5, and Eosin allowed us to generate a two channel view of the samples. Deep learning networks were employed to classify DRAQ5&Eosin fluorescent image regions into healthy and cancerous. Computationally augmented images with variable gaussian blur, Poisson noise, and resolution reduction were generated to evaluate the variability of the proposed experimental-analytical pipeline.

Results

The AI-supported framework correctly classified cancer vs. healthy tissue with an area under the curve (AUC) > 0.85. The robustness of this result was tested against a combination of induced acquisition variability and image noise/blur manipulation. AI models trained on high cancer vs healthy and low cancer vs healthy were found to be highly predictive, with accuracy decreasing for high cancer vs low cancer regions.

Conclusion

AI-based diagnostic models of prostate cancer trained on novel tissue biomarkers demonstrate robustness in cancer detection, and maintained consistent output under variations in focus, signal to noise ratio, and resolution. Overall, DRAQ5&Eosin and AI tools demonstrate strong potential in diagnostic clinical application.

Funder acknowledgement: Engineering & Physical Sciences Research Council (EPSRC)

Theme 1, Abstract 36

Abstract Contents

Identifying signal transducer and activator of transcription 3 as a therapeutic target to block extracellular matrix deposition and tumour growth in Tuberous Sclerosis Complex

Samia

S. Alzahrani1, Jesse D. Champion1 , Darius McPhail1, Mohammad A. M. Alzahrani1 , Brian L. Calver1, Elaine

Dunlop

1

, Mark Davies

1 ,

Andrew R. Tee1

1. Division of Cancer and Genetics, Cardiff University, Heath Park, Cardiff, CF14 4XN, UK

Tuberous Sclerosis Complex (TSC) is a rare genetic disorder where patients develop skin, kidney, heart and brain tumours. Tumour growth is inhibited with mechanistic target of rapamycin (mTOR) inhibitors. While stabilising disease, tumours grow back if treatment is stopped. We hypothesise that mTOR-independent mechanisms are also involved in the growth of TSC-derived tumours. To discover new disease mechanisms from transcriptomic data, differential expressed genes and enriched pathways were determined in TSC patient kidney tumour cell line with TSC2 loss of function (621-101), compared to TSC2 re-expressed cells (621-103). Western blots of key proteins and soft agar tumour formation assays were carried out to assess drug inhibitors, rapamycin, C188-9 and diacerein. In TSC2-deficient cells, we observed extracellular matrix deposition and remodelling gene enrichment. mTOR inhibition did not restore over-expression of extracellular matrix proteins (collagens, fibronectins, integrins and proteoglycans). Rather, mTOR inhibition further enhanced their expression. An interaction network mapping these enriched extracellular components featured a signalling flow bottleneck through signal transducer and activator of transcription 3 (STAT3). STAT3’s involvement was validated with STAT3 inhibitors (C188-9 and diacerein (osteoarthritis drug)), which potently repressed the expression of these extracellular matrix components. In in vitro soft agar tumour growth assays, we observed marked repression of tumour growth with both C188-9 and diacerein. STAT3 likely supports tumour growth through deposition of extracellular components in TSC-tumours. Anti-inflammatory drugs such as diacerein shows promise and could be repositioned for TSC patients as an adjunctive therapy with mTOR inhibitors.

Funder acknowledgement: Saudi Arabian Cultural Bureau (SACB) and Cancer Research Wales

Theme 1, Abstract 37

Abstract Contents

Towards Non-invasive Cancer Detection and Grading Through the Characterisation of Tissue Microstructure via Diffusion MRI

Adam Threlfall1,2, Yang Yang1,3, Emiliano Spezi4, Derek Jones1,5 , Marco Palombo1,2, Leandro Beltrachini1,3

1. CUBRIC, Cardiff University

2. School of Computer Science and Informatics, Cardiff University

3. School of Physics and Astronomy, Cardiff University

4. School of Engineering, Cardiff University

5. School of Psychology, Cardiff University

Detection of changes in tissue microstructure could lead to earlier cancer diagnosis. The two-point correlation function (S2) offers valuable statistical insights into the spatial arrangement of microstructural cells and the extracellular matrix. This could allow for the detection of changes to the morphologies of the tissue which are linked to cancer development, which could be used as a non-invasive method of grading, akin to a ‘virtual Gleason score’. This is preferable to invasive methods of grading which may even worsen patient outcomes. However, non-invasive retrieval of S2 remains difficult, particularly for complex media such as tissue microstructure.

This study investigates diffusion MRI (dMRI) as a non-invasive tool to retrieve S2. We explore the connection between the S2 of media and the dMRI signal of the extracellular matrix space, proposing that S2 could serve as a robust statistical descriptor of microstructure that is obtainable through dMRI. We generate digital phantoms, with different characteristics constants, such as long-range correlation strength, feature/structure size, and ratio of intra and extra cellular space. We demonstrate that S2 can sufficiently characterise the dMRI signal for specific types of media, as changes in S2 directly correspond to changes in the dMRI signal whilst media with the same S2 produce the same dMRI signal. Additionally, we provide a method to relate changes in the dMRI signal to S2 and, consequently, to the tissue microarchitecture. The long-term goal is to reconstruct statistically equivalent histology representations, allowing for non-invasive retrieval and analysis of tissue microstructure for easier diagnosis and grading.

Funder acknowledgement: AT was funded by Interdisciplinary Precision Oncology Cardiff Hub (IPOCH), MP was funded by UKRI Future Leaders Fellowship (MR/T020296/2), LB was funded by the BBSRC (BB/T011564/1).

Theme 1, Abstract 38

Long Read Sequencing Technologies and Lung Cancer Liquid Biopsies

Abstract Contents

Karam Aboud1,2, Joanne Morgan3, Nigel Williams3, Magdalena Meissner1,2,4, Rachel Dodds1, Sian Morgan1, Sophie Shaw1

1. All Wales Medical Genomics Service, Cardiff and Vale University Health Board

2. School of Medicine, Cardiff University

3. Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University

4. Velindre University NHS Trust

Long read DNA sequencing is fast becoming an innovative solution for the interrogation of genetic signatures in cancer samples which are hard to detect with existing short read DNA technologies. Research has demonstrated the utility for rapid detection of DNA genomic signatures. Here we directly compare the Pacific Biosciences Sequel II long read sequencing platform with the existing short read platform, for use with liquid biopsy samples from lung cancer patients (obtained from the QuicDNA study). This sample type allows for noninvasive testing of the lung cancer genetic profile at an earlier stage of the diagnostic pathway, and early data from the QuicDNA study is showing promising results that patients can access personalised treatments quicker. However, the existing testing may lack information on some types of genetic abnormalities, such as methylation signatures and copy number variants. Due to low somatic DNA quantities in these sample types, long read sequencing platforms were previously not considered as a viable solution within this clinical setting. Initial testing has shown for the first time that long read platforms can work effectively with this sample type from lung cancer patients. The ability to quantify methylation signatures has been shown. Genetic signature, such as copy number variants, not previously detectable by short read technologies, are evident. Results from this study will demonstrate the capability for identification of novel genetic signatures aligned to possible new treatment pathways, and pave the way for further exploration of alternative technologies with DNA obtained from liquid biopsies.

Funder acknowledgement: Cancer Research Wales

Theme 1, Abstract 39

Abstract Contents

Exploring a role for SLC39A zinc transporters in the dissemination of breast cancer cells

Georgia Farr1, Samuel Jones1, Kathryn M Taylor1

1. School of Pharmacy and Pharmaceutical Sciences, Cardiff University

Metastasis remains a primary cause of breast cancer-related mortality. As such, identification of molecules mediating the acquisition of highly motile/invasive phenotypes is an important area of unmet need. Members of the SLC39A (ZIP) family of zinc importers are known to be crucial drivers of mitosis and thought to play a role in epithelial-to-mesenchymal transition as well as cell migration. This study aimed to explore the contribution of these transporters to metastatic processes in clinically relevant breast cancer models, using novel monoclonal antibodies to inhibit ZIP-mediated zinc influx. Further, this study is the first to use immunofluorescence to examine specific ZIP localisation and interaction during migration, to begin to unravel the mechanism underlying this process. Antibody inhibition significantly reduced wound healing capacity and transwell migration of triple negative breast cancer cells. Immunofluorescence revealed enrichment of ZIPs to migration-related membrane structures throughout different stages of cell movement. Proximity-ligation assay was utilised to identify co-localisation of ZIP transporters with other key migration-related proteins, in order to decipher constituents of any multi-protein complexes regulating these processes. These results confirm the functional and mechanistic contribution of ZIP-mediated zinc influx to cell migration, highlighting the relevance of zinc as a central driver of metastatic processes.

Funder acknowledgement: Jenour Foundation

Theme 1, Abstract 40

Abstract Contents

Investigating the role of PREX2 in Prostate Cancer as a new avenue to sensitise to MAPK/PI3K/AKT targeted therapies

Samuel

C. Hawkins1, Boris S. Shorning1, Wytske Van Weerden2, Richard W.E. Clarkson1, Andrew D. Campbell3 , Helen B. Pearson1

1. The European Cancer Stem Cell Research Institute, Cardiff University, Cardiff, UK

2. ERASMUS Medical University, Rotterdam

3. Cancer Research UK Scotland Institute, Glasgow, UK

Prostate cancer (PCa) is the second leading cause of male cancer-related deaths in the UK. Dysregulation of the PI3K/AKT pathway, due to PTEN loss, occurs in 20% of primary and up to 50% in metastatic PCa cases, respectively. Although PI3K-targeted therapies show promise, incomplete pathway suppression leads to resistance, necessitating combination approaches to enhance their efficacy. Phosphatidylinositol-3,4,5trisphosphate-dependent Rac exchange factor 2 (PREX2), a member of the Rac GEF family, activates Rac and directly inhibits PTEN, thereby driving PI3K pathway activation. PREX2 is frequently amplified and/or mutated in various cancers such as melanoma, breast cancer, and PCa. In vivo studies in melanoma have shown that while PREX2 loss does not affect tumour growth, it sensitizes transgenic mouse and xenograft models to MEK inhibitors, similarly to treatment with a PI3Kβ inhibitor or genetic deletion. These findings raise the possibility of a similar association may be seen in other epithelial cancers including PCa. However, the role of PREX2 in PCa and its impact on PI3K pathway-directed therapies remain unknown. This project will investigate the functional significance of PREX2 in normal prostate homeostasis, tumorigenesis, and in the context of PI3K/AKT and MAPK-targeted therapies using human genomic datasets and in vitro/vivo model systems. Preliminary findings reveal that PREX2 is mutated or amplified in 3.5–4% primary and 5–23% metastatic PCa. Amplified and mutated PREX2 correlates to poorer survival. Future work will explore PREX2 as a predictive biomarker and assess whether co-targeting PREX2 and PI3K/AKT or MAPK pathway inhibitors improves therapeutic efficacy and patient outcomes.

Funder acknowledgement: Prostate Cymru

Theme 1, Abstract 41

Abstract Contents

The BioResource Data Accelerator: An all-Wales approach to sample and genomic data access serving both the rare disease and cancer research communities

Liz Merrifield1, Dr. Peter Giles1 , Dr Andrew Fry1, Rhys Vaughan1 , Prof. Richard Clarkson2, Prof. Richard Adams2, Dr. Lisa Spary2, Abigail Macarthur2 , Sian Morgan3, Dr. Joseph Halstead3, Dr Sophie Shaw3, Dr Erik Wasckiewicz3 , Joanna Zabkiewicz4

1. Wales Gene Park, Cardiff University

2. Wales Cancer Biobank, Cardiff University

3. All Wales Medical Genomics Service

4. Cardiff ECMC, Department of Cancer and Genetics Cardiff University

Cancer researchers are increasingly looking to assemble data from multiple sources (including routine NHS treatment data) and to apply advanced analytics and risk modelling to identify novel prognostic approaches from large multi-modal datasets. The BioResource Data Accelerator project works across several research infrastructure groups and NHS partners to leverage existing data, governance agreements and approaches to access consented and non-consented data, with a view to create and embed reproducible pipelines serving growing appetites for multimodal data, and delivering on national research strategies.

Wales Cancer Biobank (WCB) Digital project: partnering of the All-Wales Medical Genomics Service (AWMGS) with WCB to link existing biobank samples with routine diagnostic results, treatment, outcome and histopathology data and genomic data - a unique model in terms of UK and Welsh cancer research.

The All-Wales Genomic Databank: a new project collaboration between Wales Gene Park, Genomics Partnership Wales (GPW) and AWMGS. Providing novel routes for collecting consent for research for any patient having contact with the Genomics service widening access to consented data.

The Centre for Trials Research: partnering with Digital Health and Care Wales piloting the use of their Secure Data Environment for research. Accessing/utilising routine genomic data from the Welsh Clinical Portal to assemble control arm data for trials potentially reducing research costs.

Finally, AWMGS and WGP are working with GPW to start pilot flows of routine NHS genomic data into SAIL databank providing mechanisms to undertake data linkage for population-level research. We will present a poster and presentation highlighting work undertaken to date.

Funder acknowledgement: HCRW, Genomics Partnership Wales, ECMC, Roche

Theme1,Abstract42

AbstractContents

Telomeredysunctionand usioningliomas:deningprognosisandgenomeinstability

HarshBhatt1,2,KevnNorrs1,KezCleal1,MeganHodgson3,ChrstopherHerbert4,KathreenaM.Kuran5,WllamP.Gray 2,6,DuncanM. Bard1

1. Dvsono CancerandGenetcs,Schoolo Med cne,Card Unvers ty,Card,UK

2. Departmento Neurosurgery,UnverstyHosptalo Wales,Card,UK

3. Schoolo Med cne,Card Unvers ty,Card,UK

4. BrstolHaematologyandOncologyCentre,UnverstyHosptalsBrstolNatonalHealthServce(NHS)FoundatonTrust,Brstol, UK

5. BranTumourResearchCentre,BrstolMed calSchool,Brstol,UK

6. BranReparandIntracranalNeurotherapeutcs(BRAIN)Unt,Schoolo Medcne,Card Unversty,Card,UK

Introducton

Globlastoma(GBM) sahghlyaggressvebrantumourwthmedansurvvalo 15months.Identyngnovel markerstobetterstratypatentsandpredctresponsetotargetedtherapes saprorty.Telomeresprotect chromosome-ends romaberrantDNAdamageresponses(DDR),andtelomereerosonhasbeenshowntodrve genome nstabltyandclonalevoluton nseveralcancers.Hereweanalysedtelomerelength(TL)and  usons nGBMpatentsandrelatedth stoclncaloutcome.

Methods

146adultswthmolecularGBMshadtumourTLanalysedwthHgh-ThroughputSngleTelomereLength

Analys s.Weusedac-crcleassaytoassessunderlyngtelomeremantenancemechansms, ncludng alternatvelengthenngo telomeres.Un -andmult-varableanalyseswereconductedtoassesstumourTL mpactonOSandPFS.Sngle-moleculePCRwasusedto dentytelomere usonswhchwere urther charactersedwthlong-readnanoporesequencng.

Results

GBMsdsplayedshortenedtelomeres(medan4.0kb),unrelatedtoageatdagnossorMGMTmethylaton status.ShortTLwasnegatvelypredctve orOSonmultvarableanalyss(HR4.81,p=0.009).Thswasmore pronounced npatentswthgrosstotalresecton(HR21.55,p=0.0074).Fuson-Seqdemonstratedwdespread telomere usons nGBMsandrevealedmcrohomology,telomercdeletonsand nsertonso non-telomerc loc.Thsmutatonalspectrumsuggestsutlsatono speccDNAreparpathways nmedatngtelomere uson.

Concluson Thsstudyprovdesmechanstcevdenceo dysunctonaltelomeres nGBMs,wthTLanalyssprovdng ndependentprognostc normaton.Thepresenceo telomere usonsoersdrectevdence orsgncant genomc nstablty,potentally avourngtargetedDDR nhbtors orpatentsexhbtngthssgnature.

Funderacknowledgement:BranResearchUK,RoyalCollegeo Surgeons(England),CancerResearchWales,BRAINUK,Cancer ResearchUK

Theme 1, Abstract 43

Abstract Contents

Exploring primary lung cancer resistance using tissue and circulating ctDNA biomarkers

Karam Aboud1,2, Erik Waskiewicz2, Sophie Shaw2, Sian Morgan2, Rachel Dodds2, Rhian White2, Kirsty Hambridge2, India Tresadern2, Rob Jones3, Paul Shaw4 , Richard Adams5, Magda Meissner1

1. Cardiff University (DCG)

2. All Wales Medical Genomics Lab (AWMGL)

3. Cardiff University (DCG)

4. Velindre Cancer Centre

5. Centre for Trials Research, Cardiff

Genetic biomarkers are changes which occur within the DNA of cancer cells. These biomarkers can be used to guide personalised treatment and predict treatment response. A commonly used example from standard of care testing is the immunological marker PD-L1. Typically, genetic profiles of biomarkers focus on small, isolated changes to DNA, however measurements of microsatellite instability (MSI) and tumour mutational burden (TMB) are beginning to be utilised. These biomarkers profile a larger number of genetic changes, which when taken together produce a score that can be correlated with patient outcomes. Additionally, samples are traditionally obtained from tissue biopsies, but evidence is emerging for the utility of liquid biopsies containing circulating tumour DNA, providing streamlined, less invasive, diagnostics for patients. Here MSI and TMB have been calculated from both tissue and liquid biopsy samples from lung cancer patients recruited to the QuicDNA study by the AWMGS. Correlations have been undertaken between the two sample types, as well as direct comparisons of the measurements themselves, with additional correlation to the results of PD-L1 testing. This suite of comparative investigation aims to demonstrate the capacity to produce these scores from each sample type, and the accuracy of these measurements with regards to patient outcome. Comparisons of these measures from the two sample types shows strong correlation, indicative of liquid biopsies being a viable option for clinical testing. Furthermore, initial data from overlaying these scores with associated patient survival is promising, further indicating the potential for these biomarkers in patient care and management.

Funder acknowledgement: This PhD was funded by Velindre Cancer Centre Charitable funds and Stepping Stones charities.

Theme 1, Abstract 44

Validation of ASAH1 as a novel target for Glioblastoma

Loren, Waters1, Saul Michue-Seijas1

1. Medicines Discovery Institute, Cardiff University

Abstract Contents

Glioblastoma is the most common form of malignant brain cancer, with a poor prognosis for survival of <15 months from diagnosis. Currently, patients undergo tumour resection followed by combination radiotherapy and chemotherapy. Regardless of this multimodal approach, the aggressive and heterogeneous nature of the tumour limits success and recurrence is frequent. Emerging evidence of a cell population named glioblastoma stem-like cells (GSCs), possess a regenerating capacity that contributes to tumour aggressiveness and recurrence. Despite the significant advances in our understanding of tumour pathology, a safe, effective, brain-permeable drug treatment for glioblastoma remains elusive, highlighting an unmet clinical need. As our understanding of the mechanisms driving cancer progression and resistance advances, new potential targets are identified. Studies have shown significantly higher expression of ASAH1 and subsequently ceramide, a potent tumour-suppressor lipid metabolised by ASAH1 into sphingosine-1-phosphate (S1P), was elevated in glioblastoma cells, particularly GSC populations. Overexpression of ASAH1 has shown to reduce glioblastoma cell sensitivity to radiotherapy. Consequently, using ASAH1 inhibitors in combination therapy offers a promising opportunity. Carmofur is a potent inhibitor but is majorly limited by its selectivity and toxicity; healthy cells are also targeted, leading to adverse effects. The development of a more selective and potent ASAH1 inhibitor should enable safer and effective treatments for patients. Using an in-house, synthesised compound that has demonstrated potent inhibition and blood-brain-barrier penetrant properties, we aimed to biologically evaluate the compound potency, in comparison with carmofur, and assess growth and survival of glioblastoma cell lines, including patient-derived stem cell lines after treatment.

Funder acknowledgement: Future Leaders in Neuroscience Research (FLiNR) Seedcorn funding

Theme 1, Abstract 45

Abstract Contents

Short and long-distance communication in cancer: Feedback regulation of Ras signalling in tumourigenesis and cachexia

Shijun

Fang1, Silvia Ziliotto1, Hoi Ping Weeks1, Jack Bruton1, Fisun Hamaratoglu1

1. School of Biosciences, Cardiff University

Carcinomas originate in epithelial tissues and account for 80 to 90 percent of all cancer cases. A hallmark of carcinomas is the hyperactivating mutations in Ras signalling, which can transform a cell with the help of additional mutations. We revealed that Hippo tumour supressor pathway impinges on the transcriptional output of Ras signalling and combinatorial mutations in both pathways drive synergistic overgrowth (Pascual et al, Dev. Cell, 2017). We analyzed the transcriptional response to individual and combined modulations in Ras and Hippo signalling using RNA-sequencing. Our analysis revealed that four different negative feedback regulators of Ras signalling were highly expressed in our Ras-Hippo tumours (Pascual et al, Dev. Cell, 2017). In unpublished work, we observed that larvae that carry Ras-Hippo disc tumours exhibited wasting in distant organs, reproducing another feature of human cancer. To understand the contribution of upregulation of feedback regulation to tumour growth and cachexia, we modulated their levels in tumour background. Knockdown of three different negative feedback regulators of Ras significantly reduced tumour growth, showing that upregulation of these factors in the tumours contributed to tumour formation. This was an intriguing result given that removing an inhibitor should lead to, if anything, further activation of Ras signalling. Further, the fourth negative feedback regulator did not share this effect, indicating that knock-down of different feedback regulators have different outcomes and they may act via mechanisms other than their effect on Ras signalling. Finally and strikingly, the treatment that rescues tumour growth most effectively does not recue wasting as well as other modifications. Thus, the severity of tumour size and the degree of cachexia are uncoupled! We have generated RNA-sequencing and proteomics datasets from tumours and tumours where we knocked down expression of feedback regulators. We will present what we learnt from these analyses.

Funder acknowledgement: Ser Cymru Rising Stars Fellowship

Theme 1, Abstract 46

Abstract Contents

De-targeting species D Human Adenovirus serotype 10 and enhancing its transduction to cancer cells via fiber modifications.

Mahulena

Marušková1, Emily A Bates1, Rebecca Bayliss1 , Alan L Parker1,2

1. Division of Cancer & Genetics, School of Medicine, Cardiff University, Cardiff, Wales, UK

2. Systems Immunity Research Institute, School of Medicine, Cardiff University, Cardiff, Wales, UK

Human adenoviruses (HAdVs) are double stranded DNA viruses that can be readily manipulated and utilised as oncolytic viruses, selectively replicating in transformed cells, inducing lysis, whilst immunostimulatory transgenes encoded from within the viral genome, enhance efficacy. HAdV-D10 has an advantage of low rates of pre-existing immunity, providing a potential advantage over the commonly used HAdV-C5.

We constructed replication deficient Ad10.GFP containing an RGD motif, binding αvβ3 and αvβ5 integrins and promote virus internalisation. αvβ3 integrin is commonly overexpressed in a range of aggressive carcinomas as well as glioblastoma.

Alternatively, to target the virus into αvβ6 positive tumour cells, we incorporated the 20-amino acid peptide A20 and evaluated transduction in cancer cell lines expressing varying levels of αvβ6 integrin. αvβ6 integrin is upregulated in several epithelial carcinomas, including breast, oesophagus or pancreatic, but is undetectable on healthy epithelial cells.

The native receptor, Coxsackievirus and adenovirus receptor (CAR) is expressed widely in human body and is weakly engaged by HAdV-D10. We introduced the CAR-ablating KO1 mutation to enhance the selectivity of retargeted HAdV-D10 to alternative, cancer specific receptors.

The introduction of RGD motif into HAdV-D10 led to increased transduction of αvβ3 and αvβ5 positive cell lines whilst the introduction of A20 peptide enhanced targeting to αvβ6 positive cells. The introduction of the KO1 mutation reduced the transduction efficiency into CAR positive cells.

Our data demonstrate that the incorporation of fiber knob modifications into HAdV-D10 can enhance the selectivity of transduction of cancer cells and is well suited to precision virotherapy applications.

Funder acknowledgement: NA

Theme 1, Abstract 47

Abstract Contents

Emerging role of IGF1R in the downregulation of Kidins220-promoted disease progression of pancreatic cancer

Deepa Shankla1, Qingping Dou2, Wen G. Jiang1, Lin Ye1

1. Cardiff China Medical Research Collaborative, Division of Cancer and Genetics, Cardiff University School of Medicine, Cardiff, CF14 4XN, UK

2. Barbara Ann Karmanos Cancer Institute, Departments of Oncology, Pharmacology and Pathology, School of Medicine, Wayne State University, Detroit, MI 48201, USA

Background

Kidins220, a transmembrane scaffold protein, has been implicated in various cancers. Our recent study has revealed a reduced expression of Kidins220 in pancreatic cancer which is associated with poor overall survival and distant metastases. Knockdown of Kidins220 promoted invasiveness of pancreatic cancer cells through an upregulation of EGFR and MMP. However, the exact mechanism underlying the regulation of EGFR and possible involvement of other receptor tyrosine kinases are yet to be examined. The present study aims to investigate the involvement of other RTKs in the loss of Kidins220 related invasion and disease progression in pancreatic cancer.

Materials and methods

Pancreatic cancer cell lines MiaPaCa-2, PANC1 and AsPc-1 from ATCC were used to knockdown Kidins220 expression using lentiviral Kidins220 RNAsh, with effects compared to a scrambled shRNA control. PCR and Western blotting were employed to verify the knockdown and analyse protein expression in RTKs and their downstream signalling pathways.

Results

Following the verification of the Kidins220 knockdown in those transduced pancreatic cancer cell lines, some RTKs including PDGFRB, HER2 and IGF1R were determined using both PCR and Western blot. An increased protein level of IGF1R was seen in the both MiaPaCa-2 and ASPC1 cell lines following the knockdown of Kidins220. Perturbation of intracellular signalling downstream of IGF1R was also evident in the cells.

Conclusion

An upregulation of IGF1R was seen in the Kidins220 knockdown pancreatic cancer cell lines suggesting a potential role of IGF1R in the Kidins220 promoted aggressive cellular behaviour and disease progression which provokes further investigation.

Funder acknowledgement: NA

Theme 1, Abstract 48

Abstract Contents

Loss of bone morphogenetic proteins (BMP) and BMP receptors in gastric cancers is associated with disease progression and poor prognosis

Manal Alamri1, Yongning Jia2, Xiangyu Gao2, Ke Ji2, Shuqin Jia2, Fiona Ruge1, Wen G. Jiang1, Lin Ye1

1. Cardiff China Medical Research Collaborative, Division of Cancer & Genetics, Cardiff University School of Medicine, Cardiff, CF14 4XN, UK.

2. 4Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing), Gastrointestinal Tumour Centre, Peking University Cancer Hospital & Institute, Beijing, P.R. China

Aims

The present study aimed to examine the expression of some BMPs and their receptors (BMPR) at the transcript level in a clinical cohort of gastric cancer (GC) to evaluate their expression and the correlation between their expression and prognosis.

Methods

The transcript expression of BMPs and two receptors was examined in a clinical cohort of gastric cancer tissue samples comprising 324 primary tumour tissues and paired adjacent normal gastric tissues using real time PCR.

Results

A marked reduction was seen in the expression of BMP-3, BMP-4, BMP-6, BMP-7 and BMPR2 in the gastric tumours compared with their transcript levels in the adjacent normal tissues. In contrast to the reduced or loss of expression of those BMPs and receptor, higher transcript levels of BMP4 and BMP7 in the primary tumours were significantly associated with deaths of patients, p=0.006 and p=0.027, respectively. Higher expression levels of BMPR1B were also seen in those tumours presented distant metastases at diagnosis of the disease, median=4.1, p=0.0298 compared with the tumours without distant metastasis (median=0.5). An increased expression BMPR1B was also seen in tumours with N3 stage of lymph node metastasis, p=0.023 compared with its expression in the tumours without lymph node metastasis.

Conclusion

Transcript levels of BMP-3, BMP-4, BMP-6, BMP-7 and BMPR2 were reduced in gastric cancers. However, higher BMP4, BMP7 and BMPR1B expression levels were associated with the death or distant metastases from the disease. Further research is required for elucidate the exact roles played by these BMPs and BMPR1B in gastric cancer.

Funder acknowledgement: NA

Theme 2: Immuno-oncology

Abstract Contents

Theme 2, Abstract 1

Re-expression of MHCII in Colorectal Organoids: Investigating the novel role of EHMT1 in regulating MHCII expression

Nahla Elzefzafy1, Louise Tee1, Maria Pinna1, Neeraj Lal1, Gary Middleton2, Andrew Beggs1

1. Institute of Cancer and Genomics , University of Birmingham

2. Institute of Immunology and Immunotherapy, University of Birmingham

Background

Major histocompatibility complex class II is expressed by mature professional antigen-presenting cells, forming a critical part of the innate immune response. However, other cell types, including tumour (tsMHCII), can be induced to express MHCII in response to inflammatory signalling by IFN-g, leading to increased tumour killing. TsMHCII-II expression has been associated with a higher number of tumour-infiltrating CD4 and CD8, with improved progression-free survival (PFS) and overall survival (OS). These observations suggested that increased tsMHCII expression is associated with increased tumour recognition by T cells and enhanced antitumor immunity. However, treatment with IFN-g is not a practical solution due to patient side effects and the finding that a high percentage of tumours have no upregulation of MHCII in response to IFNg stimulation. We have recently shown that EHMT1 is a potential target to upregulate MHCII in a genome wide CRISPR/Cas9 screen. In this study, we aim to 1) investigate a potential non-canonical relationship between EHMT1 and MHC-II expression in a microsatellite stable (MSS) colorectal organoid model 2) Evaluate the ability of organoids that constitutively express MHC-II to prime naïve T cells; and 3) explore pharmacological EHMT1 inhibitors as treatments to enhance MHC-II expression in tumour cells.

Methods

CRISPR/Cas9 was used to knock down the EHMT1 gene in colorectal organoids, confirmed with Sanger sequencing and Western blot analysis. To investigate the mechanistic differences between these clones and the WT, we carried out a differential gene expression analysis using RNAseq and ChIP-sequencing, focusing on the impact of EHMT1 knockout on whole genomic methylation signatures. Furthermore, we investigated the efficacy of targeting EHMT1 pharmacologically, utilising a selection of EHMT1 inhibitors. Finally, we co-cultured EHMT1-/- clones with allogenic T cells in a mixed lymphocyte reaction (MLR) assay. T cell stimulation was evaluated by assessing CD25, CD69, CD107a, and CD137.

Results

In contrast to the wild-type (WT) organoid that showed no response to IFNg stimulation, four EHMT1-/- knockout clones demonstrated upregulated levels of MHCII expression, independent of IFNg. The level of MHCII expression by the clones was correlated with the level of methylated H3K9. Additionally, EHMT inhibitors showed variable efficacy in enhancing MHCII expression in wild-type organoids. Analysis is ongoing to investigate the capability of these clones with constitutively expressed MHCII to process and present tumor antigens to stimulate naïve CD4+ T cells.

Conclusion

This study reveals a potentially novel role for EHMT1 in modulating the tumour immune response by controlling the expression of MHC-II in colorectal organoids. Future work will focus on assessing the efficacy of combining immune checkpoint inhibitors with EHMT1 inhibitors.

Funder acknowledgement: NA

Theme 2, Abstract 2

Developing precision adenovirotherapies for glioblastoma

Emily Bates1, Rebecca Bayliss1, Mahulena Maruskova1, Alan Parker1

1. Division of Cancer and Genetics, School of Medicine, Cardiff University, Heath Park, Cardiff, CF14 4XN, UK

Abstract Contents

Glioblastoma (GBM) is a devastating form of brain cancer with poor survival rates and a significant unmet clinical need. Existing virotherapies lack the required selectivity and power to be effective in GBM. Adenoviruses (Ad) are popular vectors for a range of clinical applications. Species C, Ad5, is well documented experimentally, but its utility is limited by high prevalence of pre-exiting immunity and significant “off-target” interactions which negatively affect dose limiting toxicities. Our lab has developed the Ad5NULL platform with adverse interactions ablated. Vectors derived from adenovirus species with lower rates of pre-existing immunity are also beneficial for clinical applications. We have engineered an alternative vector based on the low seroprevalence species D, Ad10. Therefore, we have two established vectors primed for tumour selective targeting. We developed Ad5NULL-RGD and Ad10-RGD vectors which efficiently and selectively target αvβ3/5 integrins, upregulated in GBM, improving ‘on tumour’ activity and limiting detrimental off target effects. Our data indicates Ad5NULL-RGD demonstrates an improvement in transduction compared to Ad5 and Ad5-RGD. We show selective transduction in GBM cell lines and glioma stem cells (GSCs) demonstrating Ad5NULL-RGD that is well suited to GBM applications. Additionally, we demonstrate that Ad10-RGD efficiently transduces αvβ3 positive GSCs. We have evaluated these vectors in relevant models of GBM including brain organoids and patient-derived 3D cultures. We aim to develop these vectors further by incorporating transgenes that mediate tumour-specific replication and cell killing. These novel precision virotherapies hold potential as new therapeutic options for devastating brain cancers of significant unmet clinical need.

Funder acknowledgement: NA

Theme 2, Abstract 3

Abstract Contents

Localised delivery of chemoattractants and immune checkpoint inhibitors using a precision virotherapy in pancreatic cancer

Charley

Lovatt-Travers1, Luned M. Badder1, James Davies1 , Catherine Hogan2, Alan L Parker1

1. Division of Cancer and Genetics, School of Medicine, Cardiff University

2. European Cancer Stem Cell Research Institute, School of Biosciences, Cardiff University

PDAC is renowned for having an immunologically “cold” tumour microenvironment characterised by low tumour infiltrating lymphocytes (TILs), infiltration of immunosuppressive immune cells and decreased antigen presentation, and this is reflected in the poor results seen from clinical trials looking at systemic administration of immunotherapies. Immunotherapies work by driving inflammation and activating existing anti-tumour immunity; therefore, durable clinical responses are most seen in cancers which demonstrate an immunologically inflamed “hot” TME with existing immune cell infiltration. Thus, there is an unmet clinical need for combination strategies which aim to “heat up” tumours to obtain durable immunotherapy responses. To this end, oncolytic viruses (OVs), which preferentially infect and induce immunogenic cell death of cancer cells are a compelling combination agent which possess the ability to increase immune cell infiltration and overcome immunosuppression within the TME. We have previously described the modification of major capsid proteins of Ad5 to retarget the virus to αvβ6 integrin to generate a tumour-selective virotherapy; Ad5NULLA20. αvβ6 integrin is expressed in >90% of PDAC tumours, with limited expression in healthy epithelium. Here, we aim to further enhance the immune activating activity of our Ad5NULL-A20 platform by developing armed versions that locally secrete immunotherapeutic agents. Furthermore, we will aim to increase TILs through the co- expression and secretion of chemoattractants to drive infiltration of T cells and other inflammatory immune cells into the tumour. The immune stimulatory and chemoattractant capacity of these vectors will be assessed ex vivo using patient derived organoids co-cultured with patient PBMCs.

Funder acknowledgement: Pancreatic Cancer Research Fund (PCRF)

Theme 2, Abstract 4

Abstract Contents

Development of a precision immunovirotherapy expressing a bispecific immune cell engager for treatment of Glioblastoma

Rebecca J Bayliss1, Courtney Stewart1, Emily A Bates1, Alan L Parker1

1. School of Medicine, Cancer and Genetics Building, University Hospital Wales, Heath Park, Cardiff University, Cardiff CF14 4XN

Glioblastoma multiforme (GBM) is the most common and aggressive brain tumour in adults. Its high heterogeneity and ability to rapidly invade healthy cells only 5% of patients will survive more than 5 years with the average life expectancy being 12-18 months after diagnosis. Existing treatment includes surgery, radiotherapy, and chemotherapy however, complete removal of the tumour is difficult due the complexity of the disease. In this study we use an Ad5 based viral vector ablated of native tropism (Ad5NULL) and retargeted to αvβ3/5 integrins, known to be overexpressed in GBM, through incorporation of an RGD motif into the fibre region (Ad5NULL-RGD). We utilise this virotherapy to express a bispecific immune cell engager targeting T cells and a tumour antigen, over-expressed on tumour cells to induce a T-cell response at tumour sites and regress tumour growth. The efficacy of the newly developed virus was evaluated in vitro in Glioma stem cells (GSC). Expression of the bispecific construct was assessed via western blotting in various GSC, and co-culture assays were used to determine T-cell activation in the presence of the bispecific molecule in conjunction with cell viability assays to determine immune cell mediated cancer cell killing. GSC transduced with Ad5NULL-RGD expresing the bispecific and co-cultured with CD3+ T-cells show a significant increase in T-cell activation across the three lines tested. Cell viability assays showed more than 50% decrease in Glioma stem cells survival following virus transduction in the presence of T-cells Our results indicate Ad5NULL-RGD delivering an bispecific molecule leads to T-cell activation and immune mediated Glioma killing in vitro. This novel approach has the potential to become a much-needed alternative treatment option for patients with treatment resistant Glioblastoma.

Funder acknowledgement: Cancer Research Wales

Theme 2, Abstract 5

Abstract Contents

Developing pseudotyped αvβ6-integrin targeted adenovirus 5-based vectors for tumour selective virotherapy

Emma

A. Swift1, Rebecca Wallace1, Emily A. Bates1, James A. Davies1, Pierre J. Rizkallah2, Alan L.Parker1

1. Division of Cancer and Genetics, Cardiff University School of Medicine, Cardiff, CF14 4XN

2. Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, CF14 4XN

Adenoviruses are a promising source of vector backbones from which to construct oncolytic virotherapeutics. The species C adenovirus type 5 (Ad5) has been widely exploited for this purpose, but its use is hampered by high levels of pre-existing anti-Ad5 immunity. The receptor-binding fiber knob is a key target of neutralising antibodies following natural Ad5 infection. Exchanging this portion of the capsid with fiber knob proteins derived from lower seroprevalence adenoviral serotypes (such as those contained within species B and D) may thus facilitate evasion of anti-Ad5 immunity. This would also switch the primary receptor usage of the virus to that of the donor serotype. Species B and D adenoviruses have been proposed to utilise a range of broadly expressed entry receptors, all of which lack the prerequisite cancer specificity required to achieve high ontumour activity with minimal off-target effects. Here, we aimed to jointly address these issues by combining vector modifications aimed at circumventing pre-existing immunity with mutations to facilitate precision vector targeting. Knob proteins from species B (serotype 35) and D (serotypes 15, 24, 25 and 30) adenoviruses were rationally modified to incorporate the A20 peptide (which binds to the epithelial carcinomaoverexpressed αvβ6 integrin) in addition to mutations aimed at ablating endogenous interactions. These were subsequently pseudotyped onto an established native tropism-ablated Ad5 background. We have demonstrated that the resulting vectors exhibit high transduction in αvβ6-expressing cells, including in the presence of anti-Ad5 neutralising sera, indicating they could broaden the scope of patients standing to benefit from αvβ6-targeted virotherapies.

Funder acknowledgement: Cancer Research UK, Stand Up To Cancer

Theme 2, Abstract 6

Manipulating T-cell responses to improve anti-GBM immunity

Mathew Clement1,2, Sarah Lauder1, Michelle Sommerville1, Awen Gallimore1,2

1. Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, UK

2. Systems Immunity Research Institute, Cardiff University, Cardiff, UK

Abstract Contents

Glioblastoma (GBM) is the most aggressive and malignant primary brain tumour. There are limited treatment options including surgery, radiotherapy, and temozolomide chemotherapy, but these usually provide temporary relief with tumour return inevitable. Even with aggressive treatment GBM is fatal with a median survival of ~15 months and a five-year survival rate of 6.9%. This highlights the urgent need for novel treatments. Current therapeutic approaches for GBM largely fail to prevent relapse due to genetic and cellular heterogeneity within the tumour. Whilst the use of immune checkpoint blockade (ICB) or chimeric antigen receptor T-cells (CAR-T-cells) have been trialled as immune-modulators in GBM, both have failed to provide any improved tumour control indicating that other targets are needed. This may be due to other immunosuppressive mechanisms in the tumour microenvironment (TME) and/or due to sub-optimal priming of GBM-specific T-cells. The immune-modulating cytokine IL-10 plays a major role in promoting an immunesuppressive TME and has been shown to promote GBM tumour progression. CD4+ T-cells are known to release IL-10 (TH1, TH2 and Regulatory T-cells) during inflammation, however, how CD4+ T-cell mediated IL-10 release contributes to GBM progression remains unknown. My preliminary results show that IL-10 is over-produced in a mouse model of GBM and that blocking IL-10 signalling gives rise to a reduction in tumour burden, greater survival and an increase in activated immune cells in the brain. These data imply that targeted blockade of IL10 signalling could provide a useful treatment option to improve GBM outcome in humans.

Funder acknowledgement: Wales Cancer Research Centre, Systems Immunity Research Institute (Cardiff University), The Brain Tumour Charity

Theme 2, Abstract 7

Abstract Contents

Patients' experiences of cancer immunotherapy with immune checkpoint inhibitors: A systematic review and thematic synthesis

Tessa Watts1, Judit Cstontos1, Dominic Roche1

1. Cardiff University, School of Healthcare Sciences

Aim

This qualitative evidence synthesis aimed to summarize existing evidence on individuals’ experiences with immune checkpoint inhibitors (ICIs).

Background

ICIs have transformed survival outcomes for certain advanced cancers, with clinical trials demonstrating significant improvements in progression-free, treatment-free, and overall survival compared to chemotherapy (Bhramer et al., 2015; Antonia et al., 2018). Despite their obvious potential, ICIs are associated with a range of immune-related adverse events (irAEs), from mild to life-threatening (Ramos-Casals et al., 2020).

Understanding these experiences is essential to identifying support needs and ensuring effective personcentred care.

Methods

Systematic searches of MEDLINE, EMBASE, PsycINFO, CINAHL, and Web of Science identified 1,022 unique records, of which 18 qualitative and mixed-methods studies met the review inclusion criteria. Data were primarily collected via semi-structured interviews. Quality appraisal was conducted using the Critical Appraisal Skills Programme (CASP) checklist and relevant data were extracted from included papers, with themes developed through thematic synthesis (Thomas & Harden, 2008).

Results

Three analytical themes emerged: immune checkpoint inhibitor treatment decision-making; experiences and impacts of treatment; and appraisal and responses to irAEs. ICIs were broadly viewed positively due to their potential for extended survival. However, unmet needs were identified, particularly regarding information about irAEs, psychological support, and practical assistance.

Conclusion

The synthesis identifies gaps in patient information and support. Clear communication about irAEs and cancer prognosis is critical, as is addressing patients’ psychological and practical needs. Oncology professionals should ensure they have adequate knowledge to address treatment expectations and respond effectively to patients' concerns about ICIs and irAEs.

Funder acknowledgement: This study was funded by Macmillan Cancer Support (grant number 7165318).

Theme2,Abstract8

AbstractContents

Novelapproachestoreduceimmune-relatedadverseeventsassociatedwithsuccessulcancer therapy;combinedtargetingo PI3K δ andtheimmunecheckpointreceptorLAG3. SarahNLauder1,LorenzoCaptan1,AnaPres1,KathrynSmart1,MchelleSomervlle 1,AndrewGodkn1,BartVanhaesebroeck 2,Awen Gallmore1

1. Dvsono InectonandImmunty,Card Un

verstySchoolo Medcne,SIURI,Card,CF144XN,UK 2. UCLCancerInsttute,PaulO'GormanBu

ldng,Un

vers

tyCollegeLondon,72HuntleyStreet,LondonWC1E6BT,UK

TherapestargetngLAG3drectlyor ndrectlyva tslgand,FGL1,havebeenhaledasapromsngnext generatonommunecheckpont nhbtors.Analysso humanbreastcancersamplesrevealedthatboth LAG3andFGL1wereexpressedwthnthetumourmcroenvronmentmakng tanattractvecanddate or therapeutc nterventon.Wehaveprevouslydemonstratedthatpharmacologcalblockadeo PI3K δ,vathe nhbtorPI-3065, ncombnatonwthtargetedant -LAG3 mmunecheckpo ntblockaderesults nsgncant controlo tumourburden namousemodelo breastcancer.However, nhbtono PI3K δ sgnallng ntates thedevelopmento clncal mmune-relatedadverseevents(rAE)charactersedbyskn nammaton,whch s urtherexacerbatedbydsruptngtheLAG3sgnallngaxs.Topreventtreatmentrelated rAE,we ndrectly blockedLAG3sgnallngbytargetng tslgandFGL1,howeverthsapproach ntensedthedevelopmento skn erythema.Tocrcumvento -targeteectswthntheskn,ant -LAG3therapywasadmn steredlocallytothe tumouralongsdesystemcPI-3065treatment.Thsalternatvestrategymantanedareducton ntumour growth,whlstmoderatelyreducng rAEseverty.Usngan  ntermttentPI-3065treatmentstrategyprorto commencngLAG3blockade,notonlyenabledregressono over50%o treatedtumours t nhbtedthe developmento sknassocatederythemathatoccurredwthcontnuousPI-3065andant-LAG3blockade. Togetherourdatasuggeststhatetheracombnatonapproacho systemctargetngo thePI3K δ pathway andlocalsedtumour-specc mmunecheckpontblockadeor ntermttent nhbtono PI3K δ wthsystemc mmunecheckpontreceptorblockadehasthepotentaltobeawell-toleratedtherapy orsoldtumours.

Funderacknowledgement:CRUK,BreastCancerNow

Theme 2, Abstract 9

Abstract Contents

Development and Optimisation of a Patient Derived Organoid Model for T-cell Co-culture of Colorectal Cancer (CRC) in Animal-free Matrices

Chloe Harris1, Stephanie Burnell1 , Lorenzo Capitani1, Kasope Wolffs1,2, Fiona Morgan2, Paola Foulkes2, Andrew Godkin1,3, Awen Gallimore1

1. Division of Infection and Immunity, School of Medicine, Cardiff University, Heath Park, Cardiff, CF14 4XN, UK

2. Wales Cancer Bank, UHW Main Building, Heath Park, Cardiff, CF14 4XN, UK

3. Department of Gastroenterology and Hepatology, University Hospital of Wales, Heath Park, Cardiff, CF14 4XN, UK

4. Division of Cancer and Genetics, School of Medicine, Cardiff University, Heath Park, Cardiff, CF14 4XN, UK

Organoids are advanced 3D models that replicate the structure and function of human tissues, offering a valuable alternative to animal models in experimental testing and therapeutic development. We have established a biobank of matched healthy and tumour organoids from human colorectal tissue, alongside corresponding peripheral blood mononuclear cell (PBMC) samples. By integrating immune cells into these cultures, we can investigate how the immune system differentiates between malignant and healthy cells, providing key insights into selective immune targeting and tumour cell elimination. In the lab, we are carefully optimising experimental conditions for carrying out organoid, CD8+ T-cell co-culture studies, with results showing CD8+ T cell stimulation and organoid death at specific effector target ratios and peptide stimulation.

A major limitation of traditional colorectal cancer (CRC) organoid models is their reliance on Matrigel, an animal-derived matrix with undefined composition and variability. Furthermore, Matrigel can induce unwanted allogeneic CD4+ T cell responses, complicating immune co-culture experiments. To address this, we are testing a range of animal-free alternatives, including natural, synthetic, and human-derived hydrogels, to optimise conditions for CRC organoid culture and immune co-culture.

Our current results show promising progress with these hydrogels. We have validated several commercially available matrices by assessing organoid growth, viability, and the production of lactate dehydrogenase (LDH), a marker for cell damage. The LDH-based cytotoxicity assay has been successfully optimised for our organoid system and has integrated into our lab's automated organoid cell counting pipeline, ‘OSCAR.’ In addition, we have confirmed the maintenance of critical intestinal cell types Paneth and goblet cells through immunofluorescent staining, demonstrating that the structural integrity of the organoids is preserved across different matrices.

Initial results indicate that some hydrogels show minimal morphological changes and support organoid viability comparative to Matrigel. These candidates will be further tested to ensure robust performance in T-cell co-culture assays. Once validated, these gels will be used to grow organoids directly from patient tissue, creating a fully animal-free model system for studying CRC.

However, challenges remain, including optimizing ECM components to prevent the formation of ‘apical-out’ organoids, which are less suitable for immune co-culture. Despite these hurdles, we are successfully narrowing down matrices that provide an optimal balance between organoid structural integrity and immune interaction potential.

This work moves us closer to completely replacing Matrigel, with our goal being a fully humanized, animal-free CRC model system. This platform will enable precise measurement of T-cell activation, immune responses, and T-cell-mediated cancer cell death. By adhering to the principles of the 3Rs (Replacement, Reduction, and Refinement), we aim to reduce the need for animal models while supporting the development of personalized therapies and novel immunotherapeutic strategies for CRC.

Funder acknowledgement: NA

Theme 2, Abstract 10

Abstract Contents

Knockdown of hnRNPA0 Induces G2/M Arrest and reduces cell growth in acute myeloid leukaemia

Alanazi, MO1,2 , Halawi, M1,3, Hughes, OM1, Rizzo, S1, Gilkes, AF1, Yoosuf Aly, Z1 , Alruwaili, AM1,4, Knapper, S5 , Darley, RL1 , Tonks, A1 6

1. Department of Haematology, Division of Cancer and Genetics, School of Medicine, Cardiff University, Cardiff, UK

2. College of Applied Medical Science, Shaqra University, Shaqra, Riyadh 15572, Saudi Arabia.

3. College of Pharmacy, Jazan University, Jazan, Saudi Arabia

4. Medical Laboratory Technology Department, College of Applied Medical Sciences, Northern Border University, Arar 91431, Saudi Arabia.

5. Clinical Professor of Haematology, Cardiff Experimental and Cancer Medicine Centre, School of Medicine, Cardiff University, Cardiff, UK

6. Acting Head of Department of Haematology, Department of Haematology, Division of Cancer and Genetics, School of Medicine, Cardiff University, Cardiff, UK

Acute myeloid leukaemia (AML) is a clonal disorder characterised by impaired haematopoietic differentiation and unchecked proliferation. This study analysed mass spectrometry data of nuclear proteomes from undifferentiated AML blasts (FAB-M1, n=15) and normal human blood stem cells (CD34+, n=5), identifying downregulation of 13 heterogeneous nuclear ribonucleoproteins (hnRNPs), including hnRNPA0, A1, A2B1, and others. These proteins regulate mRNA processing, transport, and stability. Among the top three hnRNPs (hnRNPA0, hnRNPA3, hnRNPA2B1), mRNA expression decreased during normal haematopoietic stem cell differentiation. Analysis of publicly available datasets revealed that elevated hnRNPA3 or hnRNPA2B1 levels correlated significantly with poorer overall survival in AML patients. To evaluate hnRNPA0's functional role in AML, its expression was knocked down (shRNA) or knocked out (CRISPR-Cas9) in AML cell lines. While knockdown of hnRNPA3 did not significantly affect growth, knockdown of hnRNPA0 in Kg1a cells reduced cell growth by 61–92% (p<0.0001). Cell cycle analysis showed an increased proportion of G2/M-phase cells (control: 20.0 ± 2.0%; knockdown: 25.3 ± 1.5%) and a corresponding reduction in G1-phase cells (p<0.0001). Current transcriptomic analyses investigate how reduced hnRNPA0 expression impacts cell survival and proliferation. In summary, hnRNPA0 regulates AML cell proliferation and mRNA expression. Its knockdown reduced AML growth and induced G2/M arrest, highlighting hnRNPA0 as a potential therapeutic target.

Funder acknowledgement: Shaqra University

Theme 2, Abstract 11

Abstract Contents

Assessment of a pre-clinical adenoviral vectored cancer immunotherapy designed to harness antiviral immunity against cancer cells

Kate

Milward1, Aimee Lucignoli1, Katie Topley2, Elise Moses1, Garry Dolton2, Lucy C Jones2,3, Andrew Sewell2,4, Carly M Bliss1,4, Alan L Parker1,4

1. Division of Cancer & Genetics, Cardiff University

2. Division of Infection & Immunity, Cardiff University

3. Cwm Taf Morgannwg University Health Board

4. Systems Immunity University Research Institute (SIURI), Cardiff University

Immunotherapies, designed to improve immune responses against cancer, can be limited by lack of tumourselectivity, leading to off-target effects, or by scarcity of immunogenic tumour-associated antigens (TAAs). This study tests a novel adenoviral-vectored immunotherapy, engineered to overcome these limitations by redirecting anti-viral immunity selectively towards cancers.

Our approach exploits the tumour-selective, non-replicating Adenovirus type-5 (Ad5) platform, Ad5NULL-A20. Ad5NULL modifications eliminate native Ad5 tropisms towards healthy tissue. Insertion of A20 peptide confers tumour-tropism, re-targeting viral entry via αvβ6, an integrin enriched in aggressive epithelial cancers but not in healthy adult epithelium. To bypass reliance on TAAs, our vector Ad5NULL-A20.VA encodes a viral antigen (VA), against which a large proportion of the population exhibit T cell immunity through vaccination/infection. We hypothesised that the vector would drive cancer cells to present VA, targeting those cells for destruction by VA-specific T cells.

Following incubation with Ad5NULL-A20.VA in vitro, we quantified surface expression of VA and Human Leukocyte Antigen (HLA) in a panel of human pancreatic cancer cell lines, with varying levels of αvβ6 expression. Immunotherapy functionality was assessed in co-cultures of VA-specific T cells with Ad5NULLA20.VA-treated cancer cells, by measuring T cell activation and T cell-mediated killing of cancer cells.

VA-specific CD8+ T cells were successfully activated in the presence of cancer cells treated with Ad5NULLA20.VA, in an HLA-restricted and αvβ6-dependent manner, leading to T cell-mediated killing of cancer cells. These findings demonstrate that Ad5 NULL -A20.VA selectively infects αvβ6-expressing cancer cells and directs VA-reactive T cell cytotoxicity towards those cells.

Funder acknowledgement: Wales Cancer Research Centre; Life Science Hub Wales; Cancer Research UK; Stand Up to Cancer.

Theme 2, Abstract 12

Abstract Contents

Cell Talk: Adipocyte Derived Exosomes Promote Cell Invasion and Challenge Paclitaxel Efficacy in Ovarian Cancer

Michael Ellis Williams1, David Howard1, Claire Donnelly1, Fereshteh Izadi1, Jezabel Garcia Parra1, Megan Pugh1, Kadie Edwards1, Kerryn Lutchman-Sigh2, Sadie Jones3, Lavinia Margarit1,4, Lewis Francis1, R Steven Conlan1, Francesca Taraballi5 , Deyarina Gonzalez1

1. Swansea University Medical School, Swansea University

2. Department of Gynaecology Oncology, Swansea Bay University Health Board.

3. Department of Obstetrics and Gynaecology, Cardiff and Vale University Health Board

4. Department of Obstetrics and Gynaecology, Cwm Taf Morgannwg University Health Board.

5. Center for Musculoskeletal Regeneration, Houston Methodist Research Institute, Houston

Introduction

Epithelial ovarian cancer (EOC) is the deadliest gynaecological cancer with high mortality rates driven by the common development of resistance to chemotherapy. EOC frequently invades the omentum, an adipocyte-rich organ of the peritoneum and omental adipocytes have been implicated in promoting disease progression, metastasis and chemoresistance. The signalling mechanisms underpinning EOC omentum tropism have yet to be elucidated.

Methods

Three-dimensional co-culture models were used to explore adipocyte-EOC interactions. The impact of adipocytes on EOC proliferation, response to therapy and invasive capacity was assessed. Primary adipocytes and omental tissue were isolated from patients with ovarian malignancies and benign ovarian neoplasms. Exosomes were isolated from omentum tissue conditioned media and the effect of omentum-derived exosomes on EOC evaluated. Exosomal microRNA (miRNA) sequencing was used to identify miRNAs abundant in omental exosomes and EOC cells were transfected with highly abundant miRNAs.

Results

We demonstrate the capacity of adipocytes to induce an invasive phenotype in EOC populations through driving epithelial-to-mesenchymal transition (EMT). Exosomes secreted by omental tissue of ovarian cancer patients, as well as patients without malignancies, induced proliferation, upregulated EMT markers and reduced response to paclitaxel therapy in EOC cell lines and HGSO patient samples. Analysis of the omentum-derived exosomes from cancer patients revealed highly abundant miRNAs that included miR-21, let-7b, miR-16 and miR-92a that promoted cancer cell proliferation and protection from chemotherapy when transfected in ovarian cancer cells.

Conclusions

These observations highlight the capacity of omental adipocytes to generate a pro-tumorigenic and chemoprotective microenvironment in ovarian cancer and other adipose-related malignancies.

Funder acknowledgement: The project was funded by Health Care Research Wales (HCRW) studentship grant HS-16-38, the Medical Research Council UK Impact Acceleration Account grant (MR/X502686/1), Welsh Government ERDF SMART Expertise 2014–2022 West Wales and the Valleys grants (2017/COL/001 and 2017/COL/004), and Swansea University Texas academic partnership PhD programme.

Theme 2, Abstract 13

Abstract Contents

Preclinical Advances in Ovarian Cancer Therapy: Development of an Antibody-Drug Conjugate Targeting RAGE

Jezabel Garcia-Parra1, Claire Donnelly1, Lilianna Ordonez1, Melanie Boudaud2, Belen Pan-Castillo1, David Howard1, Emenike Onyido1, Kate Murphy3, Gilian Seaton4, Richard Clarkson4, Kerryn Lutchman-Singh5, Sadie Jones6, Lavinia Margarit7, Nadia Alfaidy2, R Steve Conlan1 , Deyarina Gonzalez1

1. Medical School, Swansea University

2. Interdisciplinary Research Institute of Grenoble, University Grenoble Alpes

3. Department of Cellular Pathology, Swansea Bay University Health Board

4. Cardiff University School of Biosciences, Cardiff University

5. Department of Gynaecology Oncology, Swansea Bay University Health Board

6. Department of Obstetrics and Gynaecology, Cardiff and Vale University Health Board,

7. Department of Obstetrics and Gynaecology, Cwm Taf Morgannwg University Health Board

Ovarian cancer (OC) is the deadliest gynaecological malignancy, ranking among the top 10 causes of cancerrelated deaths in women in developed countries. Its high lethality is attributed to late-stage diagnosis and the limited efficacy of existing therapies. Despite advancements such as PARP inhibitors and anti-angiogenic drugs, resistance and relapse remain significant challenges. Antibody-drug conjugates (ADCs) represent a promising therapeutic strategy, enabling targeted delivery of potent cytotoxic agents while minimising offtarget toxicities. However, their clinical success hinges on the identification of tumour-specific antigens with favourable expression and internalisation profiles. The Receptor for Advanced Glycation End Products (RAGE), a type-I transmembrane receptor implicated in cancer progression, has been identified as a potential ADC target. Our study confirmed RAGE overexpression in OC and its minimal expression in healthy tissues, making it an ideal target for ADC development. A panel of novel murine monoclonal antibodies was engineered into chimeric formats, and lead candidate selection was based on antigen binding and internalisation dynamics. The selected antibody was conjugated with cytotoxic payloads and evaluated for biodistribution, safety, and efficacy. Preclinical results demonstrated preferential tumour accumulation of the RAGE-targeting ADC, an improved safety profile, and significant tumour growth inhibition in vivo. This study establishes RAGE as a viable ADC target for OC and underscores the therapeutic potential of this approach in addressing the unmet clinical needs in gynaecological oncology. These findings support further development of RAGE-ADC for clinical application.

Funder acknowledgement: The project was funded by WCRC, the Medical Research Council UK Confidence in Concept grant (MC_PC_19053), the Medical Research Council UK Impact Acceleration Account grant (MR/X502686/1), Welsh Government ERDF SMART Expertise 2014–2022 West Wales and the Valleys grants (2017/COL/004), and Swansea University Grenoble academic partnership PhD programme.

Theme 2, Abstract 14

Investigation of Adenovirus Species D Serotypes as Novel Oncolytic Vectors

Rebecca

Wallace1, Emily Bates1, Rosie Mundy1, Carly Bliss1, Alan Parker1

1. Division of Cancer & Genetics, Cardiff University School of Medicine

Abstract Contents

As oncolytic viruses (OV), the species C human adenovirus 5 (Ad5) has proven popular due to its high lytic activity. Oncolytic cell death activates the immune system and allows for the initiation of an anti-tumour immune response. Furthermore, a variety of transgenes can be encoded to aid oncolytic activity. However, pre-existing immunity against Ad5 and the rapid development of anti-vector immunity following administration limit the current potential of Ad5 based OVs. Species D Ads have low pre-existing population immunity, representing a relatively untapped repository. Phylogenetically, species D Ads encompass the largest and most diverse species of Ad and might therefore be good alternative oncolytic platforms. We investigated a panel of species D Adenoviruses, including Ad15, Ad24, Ad25, Ad29, Ad30, Ad32 and Ad53 for their suitability as oncolytic vectors, using cytotoxicity, cellular tropism and viral replication as markers for good candidate viruses. Both cytotoxicity and viral replication were found to be significantly lower in species D Ads, though interestingly production of vial stock was not hindered by this. Additionally, differences in infective patterns were observed. Results indicate that species D Ads use as OVs may require further engineering and optimisation. Whilst cytotoxicity, which may induce immunogenic cell death, is a potentially advantageous trait for an OV, even higher levels of cell killing may be achieved through the expression of therapeutic transgenes. As rapid cytotoxicity may interfere with transgene expression, species D Ads may be well suited to this approach.

Funder acknowledgement: NA

Theme 2, Abstract 15

Abstract Contents

Investigating the Role of Exosomes in Antibody-Drug Conjugate Therapy: A Preliminary Study

Saoirse Wilson1,2, Claire Donelly1, David Howard1, Kadie Edwards1, Caitlin Rees1, Abdul Nagi1, Lewis Francis1, R Steve Conlan1 , Deyarina Gonzalez1

1. Medical School, Swansea University

2. Biomedical Sciences, Cardiff University

Exosomes, a subset of extracellular vesicles (EVs), may play a critical role in modulating the efficacy and safety of antibody-drug conjugates (ADCs). They are hypothesised to mediate a bystander effect, wherein cancer cell-derived exosomes carrying ADC-bound antigens induce apoptotic death in neighbouring antigennegative cancer cells, potentially enhancing therapeutic outcomes. Conversely, exosomes may contribute to resistance mechanisms by expelling ADCs or their cytotoxic payloads from resistant cancer cells, thereby reducing treatment efficacy. Additionally, cancer-derived exosomes might transfer ADC target antigens to non-cancerous cells, raising concerns about off-target effects and toxicity. In this initial study, we aim to confirm whether exosomes can indeed influence ADC efficacy and safety profiles. Using in vitro techniques, we will investigate whether ADC drugs are encapsulated within exosomes and assess their potential role in modulating ADC activity. These findings will provide foundational insights into the interaction between exosomes and ADCs, guiding future strategies to optimise ADC design, improve therapeutic efficacy, and mitigate safety concerns. This preliminary investigation is a critical first step toward understanding the broader implications of exosomes in ADC therapy.

Funder acknowledgement: NA

Theme 2, Abstract 16

Abstract Contents

Development of an Oncolytic Adenovirus platform expressing a suicide transgene to target Pancreatic Ductal Adenocarcinoma

1

Luned M. Badder1, Emily Bates

, Catherine Hogan2 , Alan L. Parker

1

1. Division of Cancer & Genetics, Cardiff University School of Medicine, Cardiff, Wales

2. European Cancer Stem Cell Research Institute (ECSCRI), School of Biosciences, Cardiff University, Wales

Pancreatic ductal adenocarcinoma (PDAC) lack validated therapeutic targets and represent an unmet clinical need. Oncolytic adenoviruses (Ad) are a promising treatment modality for PDAC, however, further work is needed to prevent dose-limiting interactions and enhance their overall potency. We have previously described the modification and retargeting of major capsid proteins of Ad serotype 5 (Ad5) to αvβ6 integrin to generate a tumour-selective virotherapy; Ad5NULL-A20. Given that αvβ6 integrin is strongly expressed in PDAC patient tumours, with limited expression in healthy adult epithelium, it is an attractive means of viral cell entry. Here, we include further modifications into our oncolytic Ad5NULL-A20 vector by incorporating “suicide transgenes” to sensitise PDAC cells to a non-toxic pro-drug.

We successfully generated an oncolytic(O) Ad5NULL-A20 vector expressing a yeast-derived fusion of cytosine deaminase and uracil phosphoribosyltransferase (FCU1), which, converts a non-toxic pro-drug 5-fluorocysteine (5-FC) to 5-fluoruracil (5-FU), a chemotherapeutic, and downstream toxic metabolites (5-FUMP). Continuous long term image-based and impedance assays were used as surrogate readouts for overall oncolytic activity in vitro and ex vivo. Our data demonstrate that OAd5NULL-A20.FCU1 in combination with 5-FC enhances overall tumour cell killing compared to OAd5NULL-A20, with high cytolysis detected in αvβ6+ pancreatic cancer cells. We further show that transduction of patient-derived PDAC organoids with OAd5NULL-A20.FCU1, in combination with 5-FC, treatment limits organoid growth and structural integrity, indicative of high levels of cytotoxicity.

Taken together, these data highlight the potential for arming a tumour selective agent with a suicide transgene and provide promising preclinical data for a novel PDAC therapeutic.

Funder acknowledgement: NA

Theme 2, Abstract 17

The Generation of an Organoid Toolkit

Abstract Contents

Stephanie Burnell1, Chloe Harris1, Lorenzo Capitani1, Stefan Milutinovic1, Carina Owen1, Julia Grimstead2, Sara Seifan2, Duncan Baird2 , Luned Badder2, Alan Parker2 , Kasope Wolffs1,3, Fiona Morgan3, Paola Foulkes3, Andrew Godkin1,4, Awen Gallimore1

1. Division of Infection and Immunity, School of Medicine, Cardiff University, Heath Park, Cardiff, CF14 4XN, UK

2. Division of Cancer and Genetics, School of Medicine, Cardiff University, Heath Park, Cardiff, CF14 4XN, UK

3. Wales Cancer Biobank, UHW Main Building, Heath Park, Cardiff, CF14 4XN, UK

4. Department of Gastroenterology and Hepatology, University Hospital of Wales, Heath Park, Cardiff, CF14 4XN, UK

Organoids are utilised in a diversity of experiments ranging from the testing of new ideas to the safety testing of novel therapies. In this project, we have generated a bank of matched healthy and tumour organoids from human colorectal tissue samples with matched peripheral blood mononuclear cell samples.

These organoids are not only available with important patient information including age, gender, location and severity of cancer but also the HLA type, MSI and mutational status of the tumour. The diversity of HLA expression aids the study of tumour escape mechanisms including interactions with T cells and NK cells. T cell killing of organoids can be measured both qualitatively and quantitatively, by observing the interactions between cells in co-culture microscopically and by analysis of organoid cell killing by flow cytometry and T cell activation by ELISA. We have obtained whole genome and RNA sequencing data from 8 matched pairs (healthy and tumour) of organoids and from this we are identifying differentially expressed genes and the mutanome for the identification of possible HLA-restricted cancer antigens. We will also use this information to understand the immune receptors and ligands that differ between healthy and cancer epithelium.

Further to this, we have developed a computational method of counting the number of cells in an organoid, which is set to become a WCRC sponsored webtool this year. This will be available to all academics working with organoids to use. Finally, we are immortalising our bank of healthy organoids using a hTERT retrovirus to prevent the shortening of the healthy telomeres. This will increase the lifespan of the healthy organoids so they can be used long-term with their tumour counterparts.

We now have a 3D in vitro model to test our in-house immunotherapeutics, including engineered T cells and small molecule inhibitors, in addition to investigations into the tumour microenvironment. We welcome collaborations from other groups that wish to work together with patient-derived organoids in the future.

Funder acknowledgement: NA

Theme 2, Abstract 18

The Urinary Microbiome Shifts in Women with Breast Cancer

Nur

Abstract Contents

Aimi Aliah Zainurin1, Matthew Hegarty1, Dimitra Ivanova1, Tim Gate3, Helen Tench4, Mandana Pennick2, Luis A. J. Mur1

1. Department of Life Sciences, Aberystwyth University, 2. Glan Clwyd Hospital, Betsi Cadwaladr University Health Board, 3. Wrexham Maelor Hospital, Betsi Cadwaladr University Health Board, 4. Bronglais General Hospital, Hywel Dda University Health Board

Introduction

Microbiomic dysbiosis could play a role in breast cancer (BC). Imbalances in microbial composition influence inflammatory pathways, disrupt immune responses, and foster a tumour-promoting environment. Our urinary proteomic and metabolomic studies suggested changes in inflammation and immunosuppression that could be linked to BC. Such changes could be reflected in the urine microbiome.

Aim

To establish if there are shifts in urinary microbiome that could be associated with BC.

Method

The study (IRAS ID: 306872) cohort involved 125 female participants with either breast cancer (BC; n=46), benign breast disease (BBD; n=36) or were symptomatic (SC; n=32) or healthy controls (HC; n=11). Urinary DNA was extracted (Fast DNATM Spin kits) and sequenced using V3/V4 16S rRNA primers on an Illumina MiSeq platform. The derived data was mined using MicrobiomeAnalyst and MetaboAnalyst platforms to assess alpha (within-group) and beta (between group) bacterial diversity.

Results

There were significant (p-value < 0.05) differences in alpha and beta diversity at genus and species levels between the groups. Some key genera have been reported to be enriched in tissue adjacent to BC tumours. Some genera encoded ß-glucuronidases and ß-glucosidases, which are implicated in oestrogen metabolism. Four genera and 12 species differed with histological BC types.

Conclusion

BC had distinct urinary-microbiome profiles from other groups and could also differentiate the BC types. These suggest discrete inflammatory/immune changes in BC which could be linked to disease progression. These findings could allow more precise and deeper understanding of BC, paving the way for new diagnostic and therapeutic innovations.

Funder acknowledgement: NA

Theme 3: Radiotherapy

Abstract Contents

Theme 3, Abstract 1

Addressing national barriers for UK clinical oncology trainees in radiotherapy research

Shannon Rowlands1, Richard Adams2,3, Jonathan Helbrow1, Daniah Thomas1, Sarah Gwynne1

1. South West Wales Cancer Centre, Swansea

2. Centre for Trials Research, Cardiff University, Cardiff

3. Velindre Cancer Centre, Cardiff

Clinical oncology trainees have strong interests in research but face significant barriers including clinical workload, infrastructure, and limited awareness of research opportunities. This project aims to enhance engagement and awareness in research by creating a research competency framework for trainees in Wales. Oncology consultants (n=13) and trainees (n=11) ranked research activities and competencies from basic to advanced to establish expectations at each training stage, including but not limited to, components of the clinical oncology curriculum. A modified delphi method involving research-active oncology consultants (n=20) provided feedback on these competencies for each training year. Forty research competencies were categorised into three groups; years 1-2, years 3-5 and research-oriented trainees. Topics include good clinical practice, writing abstracts, and higher degrees. To support trainees, initiatives such as regular teaching sessions, dedicated time in an early-phase trial unit and an online platform with access to resources such as interviews from research-active consultants are being developed. Each training site in Wales will appoint an academic representative to mentor trainees. Wales is leading the implementation of a research-activity competency framework, providing a guide for oncology trainees and the training programme. This will equip trainees with essential skills for a research-driven speciality. In view of the critical decline in academic oncologists, this initiative inspires the next generation of researchers and has the potential to transform and strengthen the national research landscape.

Funder acknowledgement: NA

Theme 3, Abstract 2

Abstract Contents

Exchange time from time-dependent diffusion-weighted MRI as a potential biomarker for treatment response in human brain metastasis

Elise Gwyther1, Sahar Iqbal2, James Powell2, Jennifer Golten2, Beat Jucker3 , Maëliss Jallais1, Derek Jones1, Chantal Tax1,5, Marco

Palombo1,4

1. Cardiff University Brain Research Imaging Centre (CUBRIC), School of Psychology, Cardiff University, Cardiff, United Kingdom

2. Velindre Cancer Center, Cardiff, United Kingdom

3. Glaxosmithkline, Pennsylvania, United States

4. School of Computer Science and Informatics, Cardiff University, Cardiff, United Kingdom

5. University Medical Center Utrecht, Utrecht, Netherlands

Introduction

Measurements of apparent water exchange time (τex) have been linked to progression in brain metastases in studies using dynamic-contrast-enhanced MRI. We used an alternative, time dependent diffusion-weighted MRI (dMRI), to infer τex without contrast agents by characterizing the diffusion time dependence of the kurtosis (K) of endogenous water molecules diffusing in brain tissue. We hypothesize that τex estimates from diffusional kurtosis time dependence can be sensitive to tumour progression and response and examine the relationship between changes of τex in brain metastasis after stereotactic radiosurgery (SRS) in a cohort of patients with different primary cancers.

Methods

20 patients with brain metastases were scanned at baseline, 1-month and 3-months. Patients received SRS between baseline and 1-month. τex, was calculated for each patient. Treatment response was assessed using RANO-BM criteria.

Results

In the good treatment response group (RANO-BM=1,2), the percentage change in τex from baseline (Δτex(%)) at 1 and 3 months was negative for all but one patient. In the poor treatment response group (RANO-BM=3,4), Δτex(%) at 1/3 months was positive, except for one patient. All patients whose cause of death was not Intracranial progression had a negative Δτex(%) at 1 or 3 months except for one patient. All the others had a positive Δτex(%) at 1 or 3 months.

Conclusion

Except for two patients with different clinical factors (necrosis/immunotherapy), Δτex(%) was associated with the RANO-BM criteria. This suggests τex could help predict response to SRS. Our cohort was small and heterogeneous; future work will apply this analysis to larger groups.

Funder acknowledgement: NA

Theme 3, Abstract 3

Abstract Contents

Cardiff University School of Medicine MRC equipment bid (2025): How a Small Animal Radiation Research Platform (SARRP) will enhance translational science across Wales and the South-West. Paul Shaw1, Stephen Paisey2, Ian Brewis3

1. Department of Clinical Oncology, Velindre University NHS Trust

2. PETIC, University Hospital of Wales and Cardiff University

3. School of Medicine, College of Biomedical and Life Sciences, Cardiff University

The Small Animal Radiation Research Platform (SARRP) is a computerised tomography (CT) guided irradiator capable of delivering targeted beam radiation to in vivo and in vitro preclinical models of cancer and normal tissue to investigate the broader impact of radiation on both normal and pathological cellular physiology. Resistance (including inflammation or damage to normal tissues) represent significant limitations. A diverse group of stakeholders within the regional research community have come together and expressed a pivotal demand for the SARRP platform. There are 8 UK centres offering the technology and none within the Wales/GW4 Research Alliance and extended South-West England regions. The combination of high[1]resolution CT imaging with the ability to support simple and complex radiation treatments using intuitive treatment planning software will enable us to truly replicate clinical treatments as a prerequisite for developing new treatment paradigms.

This platform will address bottlenecks and challenges in the translation of cancer research from early academic led projects to the clinic. We have assembled a unique collection of discovery scientists, research technical specialists, and expert radiotherapy clinicians with shared project interests aimed at addressing key translational questions of clinical relevance. Research will also focus on clinical issues unrelated to cancer, but within the MRC remit and of importance to the health of the nation. This platform will foster interdisciplinary research and help to convene researchers working with NHS networks and support research that enables the ambitions of the UK Government Life Sciences Vision to progress the translation of research into new clinical practice.

Funder acknowledgement: NA

Theme 3, Abstract 4

Abstract Contents

Benchmarking and quality assurance of a new prostate cancer brachytherapy service: prospective data collection and 2 year patient reported outcome measures

Jake Tanguay1, Jane Powell2, Alice Roebuck3, Emily Renninson1 , Donna Llewllyn4 , Katie Hook5 , Nachi Palaniappan1

1. Clinical Oncology, Velindre Cancer Centre

2. Radiotherapy Physics, Velindre Cancer Centre

3. Data and Insights, Velindre Cancer Centre

4. Radiotherapy, Velindre Cancer Centre

5. Urology CNS, Velindre Cancer Centre

Introduction

Prostate brachytherapy is an important curative treatment modality for localised prostate cancer with cure rates equivalent to surgery and radiotherapy. In 2019 a new prostate HDR (high dose rate) brachytherapy service was commissioned at Velindre Cancer Centre.

Methods

Data were collected prospectively to ensure quality and patient safety including patient disease baseline information, brachytherapy dose to structure data, patient reported outcome measures (EPIC 26 at baseline, 6 months, 12 months, 24 months and 60 months).

Results

67 patients underwent brachytherapy from 2019-2024. Baseline Cambridge Prognostic Score was 1 in 40%, 2 in 52% and 3 in 8%. Mean prostate volume 45cc. CTVpV100 dose volume constraints were achieved in 97% of cases (49% optimal, 48% mandatory). PROMS data completeness was 87%, 72%, 71% and 73% each time interval. EPIC 26 mean scores at baseline, 6 months, 12 months and 24 months were: bowel summary score92, 91, 91 and 95, sexual summary score - 79, 55, 55, 59, urinary incontinence scores 95, 93, 83, 83 and % using one or more pads per day 0, 5%, 10%, 15%.

Discussion and Conclusion

Patient selection was appropriate, dosimetrically good quality implants were achieved. The PROMS data at 24 months are in line with expected outcomes. Brachytherapy compares favourably with published surgical series (eg PACE A trial) (better sexual toxicity scoring, lower use of urinary pads, better urinary incontinence scores) and also with radiotherapy (better bowel summary scores) at the cost of a slightly worsened urinary obstructive score.

Funder acknowledgement: NA

Theme 3, Abstract 5

Abstract Contents

Advanced MRI techniques highlight distinct vascular characteristic across Glioma subtypes

Eleonora Patitucci1, Stefano Zappalà2, James Powell3, Najmus Sahar Iqbal3, Richard Wise4,5, Michael Germuska M6,7

1. Cardiff University Brain Research Imaging Centre (CUBRIC), School of Psychology, Cardiff University, Cardiff, UK

2. Cardiff University Brain Research Imaging Centre (CUBRIC), School of Computer Science and Informatics, Cardiff University, Cardiff, UK

3. Department of Oncology, Velindre University NHS Trust, Cardiff, UK

4. Department of Neurosciences, Imaging, and Clinical Sciences, University ‘G. D’Annunzio’ of Chieti-Pescara, Chieti, Italy

5. Institute for Advanced Biomedical Technologies, University ‘G. D'Annunzio’ of Chieti-Pescara, Chieti, Italy

6. Cardiff University Brain Research Imaging Centre (CUBRIC), School of Physics and Astronomy, Cardiff University, Cardiff, UK

7. Department of Radiology, University of California Davis Medical Center, Sacramento, CA, United States of America

Gliomas generate an extra blood supply to meet their growing need for nutrients and oxygen, altering normal physiology and tissue metabolism. Vascular proliferation is a pathological hallmark of gliomas, resulting in abnormal and dysfunctional vessels. In this project, we used advanced MRI techniques to detect different vascular characteristics in glioma subtypes. We acquired MRI quantitative susceptibility maps (QSM) from 27 patients (mean age 45.5±8.8 years; 20 males) diagnosed with glioma. Vascular parameters, including vessel density, vascular diameter, and oxygen extraction fraction, were extracted from the QSM maps. The group was divided according to tumour diagnosis (Astrocytoma, Glioblastoma, Oligodendroglioma) and WHO grade (low vs. high) to examine vascular differences among tumour subtypes and grades. We observed distinct metabolic and vascular characteristics across glioma subtypes, consistent with existing knowledge that more aggressive brain tumours develop their own blood supply, leading to alterations in vascular parameters. We repeated the analysis after applying a deep learning model to improve the resolution of the QSM MRI images and therefore improve the detection of the small vessels. The results were confirmed, and the statistical power of the analysis increased across all comparisons. Our findings highlight the potential of QSM maps to identify subtype-specific vascular features. Improving the resolution of QSM MRI images using deep learning provides an advantage in characterizing vascular parameters. Integrating QSM mapping into routine clinical assessments for gliomas could support tumour diagnosis and characterization.

Funder acknowledgement: NA

Theme 3, Abstract 6

Abstract Contents

A comparison of gas-free MRI methods for CMRO2 quantification in primary brain tumour

Stefano Zappalà1, Eleonora Patitucci2, James Powell3, Sahar Iqbal3 , Fabian Küppers4, Jon Shah4, Richard Wise5, Michael Germuska6

1. Cardiff University Brain Research Imaging Centre (CUBRIC), School of Computer Science and Informatics, Cardiff University

2. Cardiff University Brain Research Imaging Centre (CUBRIC), School of Psychology, Cardiff University

3. Department of Oncology, Velindre University NHS Trust

4. Institute of Neuroscience and Medicine 4, INM-4, Forschungszentrum Jülich

5. Department of Neurosciences, Imaging and Clinical Sciences, University "G. D'Annunzio" of Chieti-Pescara

6. Department of Radiology, University of California Davis Medical Center

Recent interest in finding non-invasive alternatives to PET imaging has shown the development of MR techniques for the quantification of cerebral metabolic rate of oxygen consumption (CMRO2). Their relative performance in significantly altered pathology has not been previously assessed. Three gas-free MR methodologies for mapping CMRO2 in gliomas were compared, namely: quantitative susceptibility mapping (QSM), breath-hold functional MR imaging (bhc-fMRI) and quantitative blood oxygenation level dependent BOLD (qBOLD) imaging via relaxometry. Maps of cerebral blood flow (CBF) as well as anatomical scans were acquired. Nineteen participants with a diagnosis of low- and high-grade glioma were recruited to the study (44±8.8 years, 3 females). An oxygen diffusion model describing the oxygen exchange at capillary level was used to stabilise the estimations with the bhc-fMRI and qBOLD techniques. QSM generation consisted on non-linear dipole inversion after an initial phase unwrapping and projection onto dipole fields. CMRO2 estimates from QSM and bhc-fMRI were in good agreement across grey matter (GM), white matter, oedema and enhancing tumour (ET). For these two methods, statistically significant difference between values at GM and ET were found, in line with the expected altered physiology in the tumoral area. CMRO2 estimates from qBOLD, however, showed an apparent increase at the tumoral area compared to the other methods. This could be due to the sensitivity of qBOLD to haemorrhage and iron deposits, which mask any metabolic changes. Our work suggests that QSM and bhc-fMRI techniques may be preferable to qBOLD methods where pathological iron deposits and haemorrhage are expected.

Funder acknowledgement: Wellcome Trust [220575/Z/20/Z]

Theme 4: Cancer clinical trials

Abstract Contents

Theme 4, Abstract 1

Optimising Therapy in FLT3-Mutated Acute Myeloid Leukaemia

Dolce Advani1 , Joanna Canham1, Angela Casbard1, Sylvie D Freeman2, Nicola Potter, PhD3, Abin Thomas1, Amanda Gilkes, PhD4, Sean Johnson1, Lucy Marsh1, Jane Leahy5, Hayley Timmins1, Richard Dillon, MA3, Steven Knapper, MRCP, FRCPath, DM6

1. Centre for Trials Research, Cardiff University, Cardiff, United Kingdom

2. Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom

3. Department of Medical and Molecular Genetics, King's College London, London, United Kingdom

4. Department of Haematology, Division of Cancer & Genetics School of Medicine, Cardiff University, Cardiff, United Kingdom

5. Private affiliation, PPI Representative, London, United Kingdom

6. Cardiff University School of Medicine, Cardiff, United Kingdom

Background

Substantial progress has been made in acute myeloid leukaemia (AML) treatment through innovative chemotherapy schedules and targeted therapies. FLT3 mutations occur in approximately one-third of AML patients and are associated with a high risk of early relapse (40-50% in intensively treated patients). Previous studies have identified promising therapeutic strategies, including chemotherapy intensification, FLT3 kinase inhibition, and incorporation of targeted agents like Gemtuzumab Ozogamicin (GO).

Method

Optimise-FLT3 is a phase II/III randomised three-arm, multi-stage, controlled trial comparing two experimental regimens (DA-GO-Mido and FLAG-Ida-GO-Mido) against the current standard of care (DA-Mido). Patients aged ≥16 years with newly diagnosed FLT3-mutated AML suitable for intensive therapy will be recruited from 80 UK centres and 8-10 international sites.

The primary objective is to compare event-free survival between trial arms. Events include death, failure to achieve complete remission, minimal residual disease (MRD) relapse, and frank relapse. Secondary objectives encompass complete remission rates, survival metrics, MRD negativity, toxicity assessment, and treatment resource utilization.

Patients will be randomised (1:1:1) across treatment arms, with stratification by FLT3 mutation type, NPM1 status, and age. The trial incorporates a pilot phase with safety reviews and two stages: a phase II efficacy signal assessment and a phase III confirmatory stage.

The study aims to define the optimal combination of therapeutic strategies for FLT3-mutated AML, potentially transforming treatment approaches for this high-risk patient population.

Funder acknowledgement: Funded by CRUK (Cancer Research UK)

Theme 4, Abstract 2

Abstract Contents

Collecting patient outcome data across Wales for medicines accessed via the All Wales Therapeutics and Toxicology Centre (AWTTC) One Wales Medicines process

Rosie Spears1,2, Rachel Jonas1,2, Gail Woodland1,2, Craig Barrington3

1. All Wales Therapeutics and Toxicology Centre

2. Cardiff and Vale University Health Board

3. Department of Oncology, Swansea Bay University Health Board

The One Wales medicines process enables the repurposing of medicines for conditions outside of their licence authorisation. In 2023 the All Wales Medicines Strategy Group endorsed the off-label use of dostarlimab for first line treatment of mismatch repair deficient/microsatellite unstable locally advanced rectal cancer (stage II/III) as an alternative option to chemotherapy, radiotherapy and surgery. Provision of dostarlimab for patients in Wales is on condition of provision of outcome data. In collaboration with clinical experts, AWTTC developed a collection tool using Microsoft Forms to capture clinical outcomes, safety and Quality of Life data. Data collection is ongoing and clinicians may submit data following each hospital appointment using the NHS number as a unique identifier. To permit the collection of patient identifiable data the Cardiff and Vale University Health Board Information Governance department was consulted to conduct a data protection impact assessment. An Information Sharing Agreement was prepared which has been signed by IG leads in Health Boards and Velindre Trust in Wales. This agreement allows for data to be submitted for any patient who has been treated with a medicine made available through the One Wales process. The data collection tool, alongside patient information leaflets and consent forms have been made available on NHS Wales Sharepoint. Collated non-identifiable data have been shared with the manufacturer of dostarlimab and clinicians in Wales.

Funder acknowledgement: NA

Theme 4, Abstract 3

Abstract Contents

Emma Williams and her team of research nurses and clinical colleagues are helping to encourage more nurses to get more involved in research

Emma Williams1, Katja Williams1, Jenni Davies1, Louise Jenkins1, Bethan Ingram2, Sarah Doherty3, Emily John4, Faye Blackborrow5

1. Clinical Research Group Cardiff

2. Senior Nurse

3. Advance Nursed Practitioner, Bone Marrow Transplant

4. CART Clinical Nurse Specialist

5. Advance Nursed Practitioner

Emma Williams has led the team to become more empowered to take on research projects. As nurses we are working on a number of observational studies looking at unmet needs such as pre-rehabilitation in AML patients with the PROPEL study. The MOSAICC study looking at epidemiology of Myeloproliferative neoplasms across the UK. We are the only contributing Welsh site and have Nurse PI’s and Co I’s. We have also worked on a number of retrospective and prospective studies looking at areas such as MGUS, Smouldering myeloma, CLL, and Follicular Lymphoma, some of these we have done via the commercial trials route and encouraged commercial partners to work with us via this new approach. We have more recently branched out in working with our CNS and ANP colleagues with two Anthony Nolan studies looking at quality of life issues for CART patients and their families and patients with and without cancer who are undergoing allogeneic transplants at our centre. We are also very proud to have introduced two studies into the Teenage and Young Adult unit looking at issues such as fertility after chemotherapy and outcomes of patients treated in these centres as opposed to standard healthcare settings. It’s great that our Clinicians have trust in the work that we do and also is a motivating factor for the nursing team as they feel that they are contributing to research in a more holistic way.

Funder acknowledgement: NA

Theme 4, Abstract 4

Abstract Contents

Change of study design during the feasibility part of a non-randomised multicentre study (QuicDNA) to roll out routine ctDNA testing for lung cancer in NHS Wales

Muhammad

Riaz1, Angela Casbard1, Georgina Gardner1, Margherita Carucci1, Sian Morgan3, Rachel Dodds3, Richard Adams1, Magdalena Meissner2

1. Centre for Trials Research, College of Biomedical & Life Sciences Cardiff University

2. Division of Cancer and Genomics, Cardiff University and Velindre Cancer Centre

3. All Wales Medical Genomics Services, NHS, Wales

The current standard of care (SoC) for lung cancer diagnostic pathway can take eight or more weeks. Patients with suspected lung cancer undergo a tumour tissue biopsy (SoC) for the detection of actionable genetic mutations (AMs), which are essential for treatment decisions. A new test based on blood circulated tumour DNA (ctDNA) has been developed. The QuicDNA study was originally designed with a stepped-wedge approach, multicentre non-randomised controlled trial to evaluate the implementation of ctDNA testing in patients with a high clinical suspicion of lung cancer. The design required evaluation of 1260 patients with ctDNA test and 1260 controls (SoC), with 378 (30%) expected AM patients per group. QuicDNA included a feasibility pilot: 118 patients were recruited from the first two health boards (HBs); but fewer (18.6%) than expected AMs were reported, meaning more patients were required in total. Based on information obtained in the feasibility stage, we decided to change the design to a matched cohort, utilising matched controls from routine data of lung cancer patients with AMs detected by the SoC. This new design requires a smaller sample size of patients with actionable mutations (132 in the ctDNA cohort and 132 in the SoC based historical routine data cohort). The sample size in the ctDNA cohort will be achieved from recruitment of 740 suspected stage III/IV lung cancer patients. This presentation will provide an overview of the change of the design following the completion of the feasibility pilot.

Funder acknowledgement: NA

Theme 4, Abstract 5

Evolving from Phase II into Academia’s Largest Head and Neck Cancer Trial

Abstract Contents

Christie Heiberg1, Lisette Nixon1, Christopher Hurt2, Joanna Canham1, Ceri Frayne1, Charlotte Martin1, Sean Johnson1, Mererid Evans1 , Terry M Jones3

1. Cardiff University

2. University of Southampton

3. Liverpool University

The PATHOS Phase II feasibility trial began recruiting in October 2015 with a target of 242 participants, transitioning to Phase III during 2018 following additional funding with a target of 1100. Sample size was increased relating to outcome frequencey and recruitment completed 2024, with 1349 participants enrolled. Key factors contributing to efficient site engagement and participant retention are as follows. Rigorous site selection ensured that site facilities and capacity were suitable for the trial. All departments were requested to attend the Site Initiation Visits (SIVs) which the PATHOS Chief Investigators (CIs) chaired, promoting professional relationships, establishing connections and fostering trust and rapport with site staff. Centre for Trial Research (CTR) staff provided prompt and effective support, prioritizing rapid resolution of queries to ensure smooth operations and earning the team a reputation of friendliness and reliability, as well as a Case Report Form (CRF) return rate of >90%. Regular group meetings with all collaborators kept sites updated and engaged. Positive interactions centered around ongoing appreciation of their contributions. Monthly newsletters were circulated tracking recruitment progress, celebrating top recruiters, and reinforcing engagement. Analysing regularly collected site screening logs provided valuable insights into recruitment trends and barriers. One-to-One meetings with the CI-s were arranged for sites with low recruitment, uncovering obstacles which were addressed. Participant newsletters provided updates and sustained retention by acknowledging their long-term commitment to the five-year follow-up. This multifaceted approach emphasizes efficiency, communication, and appreciation, providing a replicable framework for enhancing excellent data collection and participant recruitment and retention in clinical trials.

Funder acknowledgement: Funded by Cancer Research UK (Grant no: A25317), co-sponsored by Cardiff University and Velindre University NHS Trust

Theme 4, Abstract 6

Abstract Contents

The Evolution of GastroSCOPE – proposed as the first UK-led trial of high-dose radiotherapy for inoperable gastric cancer

Amy Case1,2, Elena Brogdan3, Lisette Nixon3, Angela Casbard3, Owen Nicholas1,2, Kieran Foley4,5,6, Gina Brown7, David Watkins1, Tom Crosby6, Richard Adams3,6, Deborah Fitzsimmons2, Ganesh Radhakrishna8, David Chuter10, Sue Campbell10, Colin Askill, Christopher M. Jones9, Christopher J Peters7 , Sarah Gwynne1,2

1. South West Wales Cancer Centre, Swansea Bay University Health Board

2. Swansea University

3. Centre for Trials Research, Cardiff University

4. Division of Cancer & Genetics, School of Medicine, Cardiff University

5. Cwm Taf Morgannwg University Health Board

6. Velindre Cancer Centre, Velindre University NHS Trust

7. Imperial College London

8. The Christie NHS Foundation Trust

9. Department of Oncology, University of Cambridge

10. Private Affiliation, Patient and Public Involvement Representative

Background:

Treatment options for inoperable gastric cancer (IGC) are limited to palliative systematic anti-cancer therapy (SACT), with low-dose radiotherapy (RT) reserved for management of symptoms such as bleeding. GastroSCOPE is proposed as the first UK-led trial of pre-emptive, high-dose RT for IGC.

Methods:

GastroSCOPE trial design has evolved following comprehensive literature review, and input from clinicians and patient representatives via:

• A series of online surveys of UK oesophago-gastric oncologists exploring perception of gastric RT, appetite for future RCTs, feedback on trial design and expressions of interest.

• Involvement of three experienced public research partners at all stages.

• Presentation at national meetings and dedicated research groups.

• Two online patient focus groups (facilitated discussion around key themes).

• Expert imaging, radiotherapy, translational and patient reported outcome measure subgroups.

Results - The resulting trial proposal:

• Maximises trial efficiency and patient accessibility via basket design of 3 distinct cohorts covering a range of IGC presentations.

• Investigates novel hypofractionated RT regimens, supported by both clinicians (92.5-100%) and patients.

• Incorporates novel, efficient statistical models including generalised pairwise comparison, with outcome measures evolving following feedback and tailored to each cohort, including progression free survival, quality of life, toxicity and incidence of stomach-related events such as bleeding.

• Includes imaging and translational research questions to increase output.

• Acknowledges issues important to patients including minimisation of visits and support with travel costs.

Conclusion:

GastroSCOPE aims to provide high-quality, randomised, practice-changing evidence for an under-studied group of patients, which following robust PPI and clinician involvement, is anticipated to lead to good recruitment once funded.

Funder acknowledgement: This work was partially funded by Wales Cancer Research Centre (AC) and Health Care Research Wales (SG).

Theme 4, Abstract 7

Abstract Contents

Hemithoracic Irradiation with Proton Therapy in Malignant Pleural Mesothelioma. UK National Proton Radiotherapy Study (NCT05655078)

P. Shaw1 , A. Gosling2, K. Durno3, C. Clarke4, C. Gardiner5, C. Hiley2,6, P. Patrick6 , N. Counsell2,6

1. Dept Clinical Oncology, VUNHST

2. UCL Hospital, London

3. Barking, Havering & Redbridge University Hospitals NHS Trust, London, UK

4. UCL, London, UK

5. University Sheffield, Sheffield, UK

6. UCL Cancer Institute, London UK

Nearly 7000 UK patients were diagnosed with malignant pleural mesothelioma (MPM) during the last Royal College of Physicians audit period (2016-2018). The use of radiotherapy with MPM has been predominantly limited to palliation, with only 15% of patients receiving any radiation. Previous trials of conventional radiotherapy to the hemithorax have resulted in toxicity (1,2). Standard of Care (SoC) systemic therapy consists of Immunotherapy (ipilimumab and nivolumab), but outcomes remain poor with a 3-year OS of <25% and limited benefit seen in patients with the most common, epithelioid, form of mesothelioma (3). As a result, deferral of systemic therapy until there is evidence of progression is an alternative SoC4. Several radiotherapy planning studies have shown the potential benefit of Proton Beam Therapy (PBT) for hemithoracic radiotherapy in patients with MPM due to a reduction in the radiotherapy dose to healthy tissues, however clinical data remains limited to single centre retrospective cohort studies (5,6). HIT-Meso aims to explore a new Standard of Care (SoC) first line treatment option to delay the need for systemic anti-cancer therapy in MPM patients suitable for surveillance by evaluating the efficacy and safety of PBT. It seeks to establish whether PBT leads to improved Overall Survival (OS) for these patients, with acceptable acute and late toxicity, and no significant impact on Quality of Life (QoL). The trial design, eligibility, methods, qualitative sub-study and current status will be reported.

References

1) Int J Radiat Oncol Biol Phys. 2006 Jul 1; 65(3):640-5 2) Int J Radiat Oncol Biol Phys. 2015 Nov 1; 93(3):606-13 3) The Lancet, 2021 Jan 21; 397(10272):375-86 4) Clin Lung Cancer. 2024 Apr 20:S1525-7304(24)00066-4. 5) Pract Radiat Oncol. 2015 Jul-Aug; 5(4):e345-53 6) Pract Radiat Oncol. 2021 Mar-Apr; 11(2):119-33

Funder acknowledgement: Asthma and Lung UK, Mesothelioma UK

Theme 4, Abstract 8

Abstract Contents

Embedding research in NHS organisation systems: Survey results of clinical ownership, support and integration of clinical trials in NHS business.

Christopher Scrase1,2,3, Carla Pothecary1, Carys Thomas4, Nicola Williams5, Tom Crosby1,6

1. NHS Wales Executive

2. Bangor University

3. Department of Oncology, Ysbyty Glan Clwyd, Betsi Cadwaladr University Health Board

4. Welsh Government

5. Health and Care Research Wales

6. Velindre Cancer Centre

Background

Cancer clinical trials provide access to innovative treatments and improve patient outcomes. However, participation and equitable access to such trials in Wales remain suboptimal, with variability across regions and organisations. Researchrich clinical settings are associated with better services and outcomes, underscoring the need to address systemic barriers to trial access. A recent thematic analysis revealed that in 2020, only 20% of patients across Wales were approached or invited to discuss participation in trials.

Purpose

This survey aims to identify challenges and opportunities to enhance participation in cancer clinical trials in Wales. Specifically, it seeks to explore whether healthcare professionals are encouraged and supported to engage in research, the visibility of research activities within organisations, and strategies to overcome barriers. The survey will inform the Tackling Cancer Initiative, a Ministerial-led programme to reduce inequalities in research access and accelerate highquality trial development.

Methods

The survey targets R&D Directors, clinicians, and healthcare professionals across Wales. Questions focus on current support for research participation, leadership in promoting trials, and organisational processes. Respondents will also be asked to propose practical solutions to common constraints, such as workforce pressures and service capacity limitations. The survey findings will be analysed to identify actionable recommendations for improving trial participation.

Results

Findings will be shared upon survey completion and will provide insights into the systemic challenges and enablers for expanding access to cancer clinical trials.

Conclusion

This survey is a critical step in delivering the Tackling Cancer Initiative. By understanding and addressing barriers to research participation, Wales can enhance trial accessibility, reduce inequalities, and improve outcomes for cancer patients across the nation.

Funder acknowledgement: NA

Theme 4, Abstract 9

Piloting a standardised variable syntax in a new skin cancer trial: SCC-AFTER

Ceri Frayne1, Casbard A1, Nixon L1, Porter C1, White A1

1. Centre for Trials Research, Cardiff University

Introduction:

Abstract Contents

A working group at the Centre for Trials Research (CTR) identified inconsistent application of variable codes names for the same variable across different cancer trials. The Group piloted a standardised variable syntax to improve the efficiency for reporting and analysis.

Methods:

The syntax was developed by Data Analysts, Data Managers and Statisticians over three meetings. The format included prefixes for form and version, and suffixes to identify: dates, primary and secondary outcomes, monitoring, and derived variables. This syntax was applied to SCC-AFTER, a phase III, randomised trial assessing the benefit of radiotherapy following excision of cutaneous squamous cell carcinoma (cSCC) skin cancer (ISRCTN54806122).

Results:

The form, version, date and derived coding raised no issues. Appending with codes for primary (_p), secondary (_s) and high-level monitoring (_t) however was impractical to code, agree, check skips and peer-review. It was agreed that any errors in the syntax application, or updates through protocol amendments which change the requirements of a suffix (e.g. high-level monitoring variable (_t) became a co-primary end-point (_p), should instead be applied by amending the data-extract code (add both _t and _p suffixes to the data-code).

Conclusion:

Strict application of the standardised variable syntax was unsuitable for SCC-AFTER. Tight timeframes during trial set-up required a pragmatic approach in balancing risk (inconsistent variable naming but reduced set-up time) vs benefit (less time spent coding exports). Establishing a standardised variable syntax framework before writing metadata is key, but application must allow flexibility. Colour-coding metadata for endpoint and monitoring variables may be more efficient.

Funder acknowledgement: NA

Theme 4, Abstract 10

Abstract Contents

Application of a practical method for eliciting prior beliefs about cancer survival in a phase 3 randomised trial of radiotherapy for patients with skin cancer

Ms Angela Casbard1, Dr Emilia Peleva2, Dr Rachel Abbott3, Dr Marisol Vazquez3, Professor Catherine Harwood2, Malavika Babu1 , Professor Agata Rembielak4,5, Mr Lincoln Tarirai Mahachi1, Dr Jerry Marsden6

1. Centre for Trials Research, Cardiff University

2. Department of Dermatology, Barts Health NHS Trust

3. Cardiff and Vale University Health Board

4. The Christie NHS Foundation Trust

5. The University of Manchester

6. University Hospitals Birmingham NHS Foundation Trust

SCC-AFTER (registration number: ISRCTN54806122) is a recently opened, randomised controlled trial of adjuvant radiotherapy (ART) after excision of high-risk primary cutaneous squamous cell carcinoma (cSCC), powered to detect a 35% reduction (hazard ratio 0.62) in the occurrence of loco-regional recurrence (LRR). The trial is open to recruitment in the UK. The trial has a frequentist analysis planned, comparing LRR-free survival in the two groups, with a recruitment target of 840 patients, but we also plan to do a Bayesian analysis. To create the Bayesian prior, we modified a template from Hiance et al (2009) to survey 30 UK experts from relevant fields (dermatology, plastic surgery, head and neck surgery, and clinical oncology) to elicit their beliefs about the benefit of ART in these patients. Experts were asked to state the LRR rate they would expect to see at 3-years post curative surgery, with and without ART. Experts were then asked to weight their level of confidence around their prediction. This provided a distribution of belief around the predicted absolute difference. Data from all 30 experts was used to create 3 expert prior distributions, the first showing the 3-year absolute difference as estimated, and two further priors which utilised the more detailed weightings given by the experts. The experts’ opinions were more optimistic, but still consistent, with our study design assumptions: e.g. the hazard ratio for the first prior was 0.54. The Hiance paper was a good introduction to formulating priors and was relatively adaptable to our trial.

Funder acknowledgement: NIHR Health Technology Assessment

Theme4,Abstract11

Managemento aComplexDataset

AbstractContents

CharlotteMartn1,Cer Frayne1,ChrsteHeberg1,ChrstopherHurt2,SeanJohnson1,JoannaCanham1,LsetteNxon1,TerryMJones 3 , MererdEvans1

1. Card Unversty

2. Unverstyo Southampton

3. LverpoolUnversty

Am:

Descrbestrateg esandbestpractcesemployedtomanageamultnatonal,complexclncaltralconducted acrosstandemdatabasestoupholddata ntegrty,protocoladherence,andtmely nsghts.

Methods:

Toeectvelymantanahgh-qualtydataset,the ollowngmethodshavebeen mplemented:

• Establshsupportverelatonshpswthstesmantanngregularcontactwthsta vaemal,phone callsandonlnemeetngs,toaddressandactondatacleanng/collecton ssuesorqueres.

• Runweeklyreportsonmssedassessmentsandhgh-leveldatabasevaldatons,topromptly ollowup wthstes.

• Manpulatedataqueryandmonthlymssngreportswth lterstogeneratetaloredreportsperCase ReportForm(CRF),varablename,orste.Thesereports dentytrends n ncompletedataandenable targeted ollow-upandprortzatono queryresoluton.

• AdaptedthemonthlymssngCRFreportcodeto ncludeco-prmaryendpontCRF’searler nthe assessmentwndow.Thspro-actvemeasuregeneratesa‘remnder’sgnaltostestocompleteths assessmentremotelyor ace-to-aceto ncreasethecompleton-rate.

• AllprortyQC ndngsarecapturedonanon-complancelog(NCL)andrevewedwththeChe InvestgatorsandSponsorto dentytrendsandagreeprortyconcernareas.Steteamsare contactedandsupportedpromptlyto mplementcorrectveacton.Thsreducesthenumbero queresrased nCentralMon torng.

Concluson:

Implementatono enhancedsystematcEDCdatamanagementprocesseshasledtoreducedmanualerrors, enablngreal-tmedatamontorng/managementtooptmsedatacollectonand ntegrty.Theseprocesses, exempled nthePATHOStral,haveyeldeda>90%CRFreturnrateandprovdedata ornumeroussubstudes.

Funderacknowledgement:FundedbyCancerResearchUK(Grantno:A25317),co-sponsoredbyCard UnverstyandVel ndre UnverstyNHSTrust

Theme 4, Abstract 12

Abstract Contents

Streamlining Cancer Clinical Trial Setup: Key Milestones, Facilitator Roles, and Strategies for Accelerated Timelines

Claire Bryant1

1. Research and Development, Velindre University NHS Trust

Setting up cancer clinical trials is a complex process requiring coordination among stakeholders to ensure timely study activation. At Velindre University NHS Trust, the setup involves contributions from Principal Investigators (PIs), Research Nurses, internal Support Departments (e.g. Pharmacy, Radiology, Radiotherapy), and external Service Providers offering specialist services such as specific tests, scans, or biopsies. Additionally, contributions are required from Research Setup & Delivery staff play a crucial role in governance, finance review, data management, and trial coordination. For trials conducted at Velindre Cancer Centre, the process is facilitated by the Research Service's "Research Facilitator." Facilitators will work closely with PIs, Sub-Investigators (Sub-Is), research nurses, internal support departments, external service providers and setup/delivery staff. Their responsibilities include assessing resources and determining whether we have the capacity and capability to undertake the trial. Facilitators ensure that all preparations are in place to enable trial participant screening and recruitment to begin promptly, once formalities such as Contracts and Confirmation of Capacity and Capability are completed. All these factors impact the timings to progress from site selection to sponsor “Greenlight” to Open. This poster will detail key milestones of study setup, from site selection to receiving the Sponsor's “Greenlight” to open the trial to recruitment. It will also highlight considerations for Research Facilitators during resource and capacity assessment and what factors contribute to a timely study activation. The poster will also include a QR code inviting conference attendees to provide feedback on factors influencing trial setup timelines, challenges encountered, and strategies to overcome them

Funder acknowledgement: NA

Theme 5, Abstract 1

Theme 5: Palliative and supportive oncology

Abstract Contents

Barriers to and facilitators of access, acceptability and adherence to cancer prehabilitation: a mixed methods systematic review

Dr Tessa Watts1, Dr Nicholas Courtier1, Dr Sarah Fry1, Dr Nichola Gale1, Elizabeth Gillen1, Dr Grace McCutchan2, Manasi Patil1, Tracy Rees3, Dr Dominic Roche1, Dr Sally Wheelwright4, Professor Emirata Jane Hopkinson1

1. School of Healthcare Science, Cardiff University

2. Division of Population Medicine, Cardiff University

3. Velindre Oncology Academy, Velindre University NHS Trust

4. Brighton and Sussex Medical School, University of Sussex

Introduction

Prehabilitation aims to prepare people for cancer treatment and enhance treatment outcomes by supporting physical activity, nutrition and emotional resilience. People from some minority ethnic groups and socioeconomically deprived communities are under-represented in prehabilitation interventions. To enhance equitable cancer prehabilitation, knowledge of facilitators of and barriers to engagement is needed. This mixed-methods systematic review aimed to identify the facilitators of and barriers to access, adherence and acceptability of cancer prehabilitation.

Methods

Eight electronic databases and grey literature were systematically searched for empirical studies published in English between January 2017 and June 2023. Screening, data extraction and critical appraisal for included studies were conducted by two reviewers independently using Covidence software. Methodological quality was assessed using the Mixed Methods Appraisal Tool. Quantitative and qualitative data were analysed independently and synthesised thematically.

Results

Searches identified 11,604 records and 56 international studies of variable methodological quality were included. Analysis identified facilitators and barriers of access, adherence and acceptability of prehabilitation interventions at individual, intrapersonal and structural levels. No study reported analysis of barriers and facilitators to prehabilitation specific to people from ethnic minority communities and one study described health literacy as a barrier to access for people from socioeconomically deprived communities.

Conclusions

Limited research about barriers and facilitators in deprived and ethnically diverse communities suggests this is a research priority. To enhance the inclusivity of cancer prehabilitation, adjustments may be needed to accommodate individual characteristics and attention given to structural factors. Interpersonal connections are proposed as a fundamental ingredient for successful prehabilitation.

Funder acknowledgement: NIHR

Theme 5, Abstract 2

Abstract Contents

A service improvement project assessing the current practice for discharge letter documentation within a specialist oncology hospital.

Dr. Caitlin Cahill1 , Professor Nikki Pease2

1. Junior Clinical Fellow in Palliative Medicine, Velindre University NHS Trust

2. Professor of Palliative Medicine, Velindre University NHS Trust

Introduction

The GMC states as part of providing a good standard of care “you must promptly share all relevant information about patients with others … involved in their care” (GMC, 2024). As oncology treatments become more specialised it is imperative that information pertinent to patient care is shared across care setting. This is especially important when patients have required an admission. This service evaluation explores how discharge advice letters (DALs) are generated by doctors within a tertiary oncology hospital.

Methods

50% (n=7) of resident doctors working in a regional specialist oncology centre were interviewed individually to ascertain the current process of DAL production. A semi-structured interview technique using the following three questions was followed.

• Who can add information to a DAL?

• Who most commonly does write a DAL?

• What information or resources do you use to write a DAL?

The interviews were recorded, transcribed and a thematic analysis of interviews conducted to understand the processes, challenges, and potential improvements regarding DALs.

Results

Themes identified:

1. The professional cohort who commonly perform the completion of DALs.

2. Common sources of information used to complete a DAL, including treatment escalation plans, DNACPR forms and treatment intent.

3. Training gaps and inconsistent practice.

4. Current systemic barriers.

5. Suggestions for potential improvements.

Conclusion

The thematic analysis identifies the need to reduce inconsistency in medical documentation through structured frameworks and systemic changes for resource management to improve patient care. Further improvements were suggested which require assessment for feasibility.

Funder acknowledgement: NA

Theme 5, Abstract 3

Nurses' experiences of caring for people with cancer in a general hospital setting

Karen Gillespie1 , Jeorgia Greenfield1 , Dr Tessa Watts2

1. Acute Oncology, Cardiff and Vale UHB

2. School of Healthcare Sciences, Cardiff University

Introduction

Abstract Contents

For many reasons, acutely unwell people with cancer do present to general hospitals. As such, nurses in these settings, who may not have any cancer care education and training, will regularly care for people with cancer. There is extensive evidence of specialist oncology nurses’ experiences of caring for cancer patients. However, research exploring registered, adult field, nurses' experiences of caring for these patients is limited. Accordingly this study aimed to gain insight into the experiences of adult field registered nurses caring for people with cancer in an acute hospital setting in order to obtain insight into their education and support needs.

Method

A qualitative, exploratory approach was adopted using one-to-one semi-structured interviews with five registered nurses (adult field) with experience of caring for people with cancer in acute hospital settings. Data were collected in January 2024, transcribed verbatim and analysed using reflexive thematic analysis.

Findings

The analysis identified three core themes: Nurses’ experience of caring for cancer patients in acute care settings; the challenges of caring for these patients and the educational needs of nurses caring for cancer patients in acute care settings.

Conclusion

Nurses working in acute hospitals care for patients with cancer regularly. Barriers such as time constraints, environment and heavy workloads were identified, along with the need for better understanding of oncological emergencies, cancer treatments and their management. Upskilling the nursing team to enable them to feel better equipped to support cancer patients needs to be a priority. Further research in this area would be beneficial.

Funder acknowledgement: NA

Theme 5, Abstract 4

Abstract Contents

Implementation of cancer-specific Holistic Needs Assessment (HNA) tools in clinical practice and their applicability to the brain tumour population; systematic review and narrative synthesis.

Sivell S1, Mann M1,2, Hamilton T3, Baddeley E1, Byrne A4, Retzer A5

1. Marie Curie Research Centre, Division of Population Medicine, Cardiff University

2. Specialist Unit for Review Evidence, Cardiff University

3. Palliative Care, Aneurin Bevan University Health Board

4. Velindre University NHS Trust

5. Centre for Patient-Reported Outcomes Research & NIHR Applied Research Collaboration West Midlands, Institute of Applied Health Research, University of Birmingham

Background

Gliomas - the most common type of malignant brain tumour - have an unpredictable and variable trajectory ranging from tumours curable by surgery to aggressive glioblastoma. People with glioma can experience challenging neurocognitive and practical unmet needs, necessitating support to cope with the effects of glioma and its treatment. Holistic Needs Assessment (HNA) is a structured approach to address the needs of cancer patients and may be appropriate for people with glioma.

Aims

To identify and review any brain tumour specific HNAs and the clinical implementation of HNAs in any adult cancer population.

Method

Five databases were searched using text words and medical subject headings from 2008 to until March 2023. Reference lists of systematic reviews were checked for relevant studies. Two independent reviewers independently performed study selection, critical appraisal, and data extraction.

Results

Six HNA tools implemented in clinical practice, across 8 studies were identified. One HNA (n=1/6) was adapted for brain tumour patients. There was limited consensus on timing, location and mode of delivering HNA tools in practice. Patients were more likely to report on physical rather than psychosocial needs, with limited evidence of patient and staff satisfaction with HNA use.

Conclusion

There is limited academic evidence of HNAs being successfully implemented in brain tumour and the wider cancer healthcare settings. A wider scope of what outcomes, how and by whom are being used to assess the needs of glioma patients in routine clinical practice is needed to develop and implement consistent tools to improve patient care.

Funder acknowledgement: NA

Theme 5, Abstract 5

Abstract Contents

Informing the definition of Future Care Planning within end of life care: a scoping review of the literature.

Sivell S1, Mann M1,2, Hackett R3, Harding E4, Taubert5

1. Marie Curie Research Centre, Division of Population Medicine, School of Medicine, Cardiff University

2. Specialist Unity for Review Evidence, Cardiff University

3. Velindre University NHS Trust and City Hospice Palliative Care Team, Cardiff

4. Velindre University NHS Trust, Wales

5. School of Medicine, Cardiff University

Background

Future Care Planning (FCP) is an umbrella term being increasingly applied in palliative care and has been adopted as part of several national strategies, including NHS Wales and has been advocated by patient/carer advocates in Wales as a more understandable term than advance care planning. A clear and consistent definition of Future Care Planning would support health and social care professionals working in frailty and palliative care.

Aims

• To scope and identify definitions of ‘Future Care Planning’ in the existing literature;

• To describe what a ‘Future Care Plan’ is, with regards to end-of-life care and advance care planning, should look like and incorporate.

Methods

Palliative care Evidence Review Service (PaCERS) methodology with modifications relevant to scoping reviews were used. Four key databases were searched from1999-July 2024 for relevant published papers. Supplementary sources have also been checked for appropriate studies.

Results

Twenty-one articles reporting on FCP. FCP is identified to: work with health and social care professionals to consider what matters most to them nearer the end of life; is relevant to those with diminishing capacity for decision making; does not typically carry binding legal status; include care plans which should be recorded and shared with all relevant stakeholders.

Conclusion

We identified a variety of definitions, acronyms and complexities to the definition of FCP across, providing a much-needed assessment of FCP and inform a Once for Wales approach to FCP.

Funder acknowledgement: NA

Theme 6: Population health-based cancer prevention and early diagnosis

Theme 6, Abstract 1

A Third Sector Campaign to Increase Symptom Awareness of Oesophageal and Stomach Cancer in Wales

Madeleine

Young1 , Stephanie Jones2, Hasan Habibi3, Catrin Hallert1, Greg Pycroft1 , Lowri Griffiths1

1. Tenovus Cancer Care

2. Bath University

3. Cardiff and Vale Health Board

Whilst cancer survival rates continue to improve amongst most cancer types, 6 cancer types categorised as “Less Survivable Cancers” remain associated with poor prognosis. Of these 6 cancer types in Wales, there is limited activity in the fields of oesophageal and stomach cancer. We published “A Burning Issue”, an in depth report on the subject, which identified that lack of symptoms awareness, particularly amongst the groups most at risk (including older men, living in areas of higher deprivation) was a big driver of late diagnosis. In order to raise symptom awareness and potentially improve early diagnosis rates amongst these cancer types we focused on engaging with local pharmacies to encourage conversations with community members who frequently purchase over the counter medication to treat common symptoms of oesophageal or stomach cancer such as heartburn and acid reflux. To achieve this we utilised a post-code lookup to identify pharmacies in Wales which were located in the 10% most deprived areas as according to the Welsh Index of Multiple Deprivation where we shared information, posters and symptom awareness cards. Alongside the activities with pharmacies we also ran a printed campaign with local media within more deprived areas and a social media campaign including a video of a leading consultant reiterating the need for earlier diagnosis. This activity ran for 1 month during which time we estimate our symptom awareness information was viewed more than 4.5million times, and resulted in more than 6,000 visits to our website which held more detailed information about symptoms.

Funder acknowledgement: NA

Theme 6, Abstract 2

Abstract Contents

Current Landscape of Drug approvals for Genitourinary (GU) Cancers in North America and Europe. Jose C. Tapia1, Javier Gavira2, Diana Matthews1, Matteo Santoni3, Matthew Young4, Louis Blondel5, Ronan Flippot2, Ricky Frazer1, Georgia Anguera6, Pablo Maroto6

1. Velindre Cancer Centre, Velindre University NHS Trust, Cardiff, Wales, United Kingdom

2. Medical Oncology Department, Institut Gustave Roussy, Paris Saclay University, Villejui, France

3. Oncology Unit, Macerata Hospital, via Santa Lucia 2, 62100, Macerata, Italy

4. Barts ECMC, Barts Cancer Institute, Queen Mary University London, London, United Kingdom

5. Institut Gustave Roussy, Paris Saclay University, Villejui, France

6. Department of Medical Oncology, Hospital de la Santa Creu I Sant Pau, Barcelona, Spain

The landscape of drug approvals for genitourinary (GU) cancers varies significantly across high-income countries. This study examined approvals for prostate cancer (PC), renal cell carcinoma (RCC), and urothelial carcinoma (UC) in the United States (US), Canada (CAN), France (FRA), the United Kingdom (UK), Spain (SPA), Italy (ITA), and Portugal (POR) from December 2005 to March 2024. We reviewed regulatory labels and reports, collecting data on approval dates, trial characteristics, efficacy, toxicity, and quality of life. Time-to-approval (TTA) was calculated for each indication relative to US approval, and substantial clinical benefit (SCB) was assessed using ESMO-MCBS criteria. Of 55 approved indications, 36% were for PC, 36% for RCC, and 28% for UC. Only 55%, 40%, and 47% met SCB criteria for PC, RCC, and UC, respectively. The US, CAN, and FRA approved ≥75% of total PC and RCC indications; only the US met this threshold for UC. Similarly, the US, CAN, and FRA approved ≥75% of SCB indications for PC and RCC; for UC, this was limited to the US. TTA <12 months was achieved for PC in CAN, FRA, and SPA; for RCC in CAN and FRA; and for UC only in CAN. The US, CAN, and FRA led in GU cancer drug approvals, but only about half of these met SCB criteria. CAN and FRA consistently achieved shorter TTA following US approval, while the UK, SPA, ITA, and POR showed greater heterogeneity. UC had the fewest approvals outside the US.

Funder acknowledgement: NA

Theme 6, Abstract 3

Abstract Contents

Disparities in Urothelial Carcinoma (UC) Drug Approval: Contrasting North America and Europe

Jose C. Tapia1, Javier Gavira2, Diana Matthews1, Matteo Santoni3, Matthew Young4, Louis Blondel5, Ronan Flippot2, Ricky Frazer1, Georgia Anguera6, Pablo Maroto6

1. Velindre Cancer Centre, Velindre University NHS Trust, Cardiff, Wales, United Kingdom

2. Medical Oncology Department, Institut Gustave Roussy, Paris Saclay University, Villejui, France

3. Oncology Unit, Macerata Hospital, via Santa Lucia 2, 62100, Macerata, Italy

4. Barts ECMC, Barts Cancer Institute, Queen Mary University London, London, United Kingdom

5. Gustave Roussy, clinical pharmacy department, Villejuif, France

6. Department of Medical Oncology, Hospital de la Santa Creu I Sant Pau, Barcelona, Spain

Background

The global landscape of urothelial carcinoma (UC) drug approvals is marked by variability. This study analyzed UC drug approval characteristics in North America and Europe.

Methods

We reviewed UC drug approvals in the United States (US), Canada (CAN), France (FRA), the United Kingdom (UK), Spain (SPA), Italy (ITA), and Portugal (POR) from December 2005 to March 2024. Regulatory labels and reports were analyzed for approval dates, trial characteristics, efficacy, toxicity, and quality of life (QoL). Substantial clinical benefit (SCB) was assessed using ESMO-MCBS criteria.

Results

Since February 2017, 15 indications have been approved (Table 1). Most supporting trials were single-arm (57%), open-label (93%), and phase 3 (60%). Overall survival (OS) was the primary endpoint in 46%, with QoL evaluated as secondary or exploratory in 20% and 26%, respectively. Only 40% demonstrated OS benefit, and none showed QoL improvement. SCB was identified in 46%. All countries approved second-line antiPD-1/PDL1 therapies and first-line maintenance avelumab (AVE). Adjuvant nivolumab (NIVO) was not approved in POR. Immunotherapy for platinum-ineligible patients was approved in the US, CAN, and the UK. Third-line therapies erdafitinib (ERDA) and enfortumab vedotin (EV) were approved in 3 and 4 countries, respectively. Only the US approved non-muscle invasive bladder cancer (NMIBC) therapies. SCB approvals were led by the US (100%), CAN (71%), and FRA (71%).

Conclusion

The US leads in UC drug approvals, followed by CAN and FRA. Significant disparities exist across Europe, even for drugs with SCB, with most approvals lacking evidence of OS, QoL, or SCB.

Funder acknowledgement: NA

Theme 6, Abstract 4

The Epidemiology of Cancer and Cardiovascular Disease Diagnosis in the UK

Caitlin Partridge1, James Rafferty1, Keith R Abrams2, Rhiannon K Owen1

1. Department of Health Data Science, Swansea University

2. Department of Statistics, University of Warwick

Background & Objectives

Abstract Contents

Cancer and cardiovascular disease (CVD) are two of the largest causes of death in the UK. Additionally, individuals with multiple long-term conditions (multimorbidity) have a higher mortality rate. This research aims to describe the epidemiology of cancer and CVD diagnosis and understand the diagnosis process in terms of timing, setting and ordering of cancer and CVD diagnoses using population-scale, linked anonymized electronic health records (EHRs) in people with multimorbidity.

Method

We used multi-state models to map the diagnostic pathway for cancer and CVD, consisting of 12 possible states including first and second diagnoses, and setting including emergency department (ED) and a non-ED diagnoses. Summary statistics were produced from population-scale, linked EHR data for 1,092,999 individuals in Wales over a 15 year period following a 5 year clearance period.

Results

Statistics were found for proportion of individuals in each state, alongside demographics such as sex, age, Welsh Index of Multiple Deprivation (WIMD) quintile and rural or urban location. Individuals with a first diagnosis of cancer or CVD both had larger proportions of individuals diagnosed at in a non-ED setting, 204,666 (84.2%) of cancer diagnoses and 146,213 (52.5%) of CVD diagnoses. The proportion of individuals with a second cancer or CVD diagnosis in a non-ED setting decreased by 6.0% and 2.3% respectively.

Conclusions

Further multi-state models will be used to assess the probability and rate of subsequent diagnoses and death. They will explore the impact of covariates such as socio-demographic characteristics on diagnostic pathways and associated outcomes.

Funder acknowledgement: HDR UK

Theme 6, Abstract 5

Abstract Contents

How can we equitably support people if self-sampling becomes a part of cervical screening?

Foundations for a decision SUpport intervention to support Choice in Cervical scrEEning moDality (SUCCEED)

Dr Eleanor Clarke1 , Dr Denitza Williams1 , Dr Kate J Lifford1 , Lindsay Haywood2 , Prof Fiona Wood1 , Prof Jo Waller3 , Prof Adrian Edwards1 , Dr Natalie Joseph-Williams1 , Dr Caroline Evans2 , Gareth Powell4 , Dr Rhiannon Phillips5 , Prof Andrew Carson Stevens1 , Dr Katie Walbeoff4 , Dr Ardiana Gjini6 , Prof Kate Brain1

1. Cardiff University

2. PPI Partner

3. Queen Mary University of London

4. Public Health Wales

5. Cardiff Metropolitan University

6. Hywel Dda Health Board

The Problem

In the UK, people with a cervix aged 25-64 years are offered NHS cervical screening (CS) through clinician sampling for high-risk Human Papillomavirus. However, uptake is suboptimal and cervical cancer is the second most diagnosed cancer in CS-eligible individuals under age 45 years. Soon this population could be offered at-home self-sampling as an alternative to clinician CS. This offer requires careful planning to support equitable and informed person-centred participation.

The Approach

Qualitative semi-structured interviews with a diverse sample of CS-eligible individuals (n=30) and stakeholders (n=23) were conducted, underpinned by relevant behaviour change and decision support theories. Interviews explored communication preferences, decision support needs for choice in CS, system implications, cultural sensitivities and implementation of interventions for choice in CS. Interviews were transcribed verbatim and thematically analysed.

Findings

Four main themes across both participant groups were identified:

• Misunderstanding of clinician-led CS screening: Many participants did not understand the current clinician CS test, despite feeling they do.

• Attitudes: Although choices in healthcare were welcomed, some expressed cynicism regarding the agenda behind CS changes.

• Communication launch preferences: Participants raised the need to tailor and target public health messages about CS choice in order to reach different populations.

• Decision support needs: To enable people to make informed choices, reassurance is needed that they could carry out their own self sampling as effectively and safely as clinician sampling.

Consequences

A novel theory-informed logic model has been developed to identify the key mechanisms of an intervention to support equitable, informed choice in cervical screening.

Funder acknowledgement: Cancer Research UK

Theme 6, Abstract 6

PROSTAD: Development of a Model Prostate Cancer Diagnostic Pathway

Savita Shanbhag1, Rachel Gemine2, Stephen Farrington3, Yeung Ng4, Chris Hopkins3

1. Medical Directorate, Hywel Dda University Health Board

2. NHS Wales Joint Commissioning Committee

3. TriTech Institute & Innovation, Hywel Dda University Health Board

4. Urology Department, Hywel Dda University Health Board

Background

Abstract Contents

Prostate cancer is the most common cancer among men in the UK. Despite Welsh Government targets for 75% of patients to start treatment within 62 days of referral, waiting times across Wales often fall short. The Hywel Dda University Health Board (HDdUHB) Urology Department, in collaboration with the Tritech and Innovation Division and Swansea University, conducted extensive process-mapping to identify factors contributing to these delays. They found deficiencies in the pathway, compared to the optimal national pathway, related to initial patient communications, MRI capacity and reporting, pathology capacity, and outpatient clinic waits.

Aims and Methodology

The PROSTAD project aimed to develop an optimal patient diagnostic pathway through workforce and planning reorganisation, incorporating gold standard diagnostic and investigative techniques (multi-parametric MRI). The goal was to reduce the time patients spend in the pathway. With support from patient and public involvement, the project sought to understand barriers at the front end of the pathway, including implementation challenges, and identify facilitators that speed up progress to improve patient communication, experience, and outcomes. A weekly prostate-specific MRI scanning session, with reporting within 24 hours was established.

Results

The PROSTAD pathway reduced the time from referral to MRI to 7 days (n=127), with reporting 1 day later. In comparison, patients on the non-PROSTAD pathway waited 22 days (n=112) from referral to MRI, with reporting 14 days later. Impact The PROSTAD pathway significantly reduced diagnostic delays, enhancing patient outcomes and experience. Its replicability across Wales could improve care for suspected prostate cancer patients nationwide.

Funder acknowledgement: Cancer Research UK

Theme 6, Abstract 7

Abstract Contents

Acceptability and accessibility of using a peer-led WhatsApp group for sharing prostate cancer risk information: protocol for a pilot study for proof of concept

Dr Sarah Fry1 , Dr Shancang Li2 , Dr Georgios Theodorakopoulos2, Dr Nicholas Courtier1, Dr Harriet Quinn-Scoggins3

1. School of Healthcare Sciences, Cardiff University

2. School of Computer Science and Informatics, Cardiff University

3. School of Medicine, Cardiff University

Background

Prostate cancer is the most diagnosed tumour in men and the fifth leading cause of cancer-related deaths worldwide. Black men and those with a family history of prostate cancer are at the highest risk, yet diagnosis rates among black men remain low. Previous research in Wales has shown that for black men, sharing prostate cancer risk information amongst their community groups could increase awareness, with the potential for early detection and diagnosis.

Aims

This pilot study will evaluate the acceptability and accessibility of a novel peer-led WhatsApp community as an intervention to disseminate prostate cancer risk information.

Method

An explanatory sequential mixed-methods design will be used with up to fifty participants. Guided by two public contributors (PCo’s), participants are being recruited amongst the friendship groups of the PCo’s and invited to a WhatsApp group to view risk messages. Quantitative data will be collected using a survey based on the Sekhon Theoretical Framework of Acceptability and the EHeals health literacy scale. Subsequently, semistructured interviews will be conducted with up to twenty purposively sampled participants from the WhatsApp group to further explore survey responses. Accessibility data will be gathered using a unique study URL to track the proportion of participants accessing the Prostate Cancer UK Risk Checker, and by evaluating the privacy and security features of WhatsApp. We will present the protocol of our novel approach to sharing prostate cancer risk information and the methods to investigate the accessibility and acceptability of sharing cancer risk information in this way.

Funder acknowledgement: Cancer Research UK

Theme 6, Abstract 8

Abstract Contents

Insights, challenges and opportunities for cancer clinical care, workforce, innovation and research in Wales from the HIWBRIS Study (Healthcare Innovation, staff Wellbeing and Burnout: Researching Interactions and Solutions; IRAS 346499)

Dr Mick Button1 , Jennet Holmes2 , Dr Tom Howson3 , Dr Roderick Thomas4 , Professor Nick Rich4

1. Medical Directorate, Velindre Cancer Services, Velindre University NHS Trust

2. Innovation Lead, Velindre University NHS Trust

3. Bevan Commission

4. School of Management, Swansea University

Innovation and research are essential for healthcare to inform and ensure optimal short and long-term best practice. The burnout crisis in healthcare impacts staff health and the quality of care received by patients. Oncology may be an exemplar of this challenge, given its dynamic clinical nature, ever increasing treatment demands/complexity, coupled with workforce and resource limitations, highly emotive clinical work and high levels of burnout. Innovation can create positive solutions; but may have positive and negative interactions with wellbeing/burnout. The relationship between staff wellbeing/burnout and innovation is not well researched in healthcare, a potentially important omission given the need for innovation and the high prevalence of burnout. The HIWBRIS mixed methods research study (Sponsor: Velindre University NHS Trust) explores this knowledge gap to inform/implement practical solutions to create “the right environment for innovation” for current and future clinical models. We present our research approach, initial exploratory quantitative data (gathered from NHS Wales staff; highlighting potential interactions, missed opportunities and areas for improvement) and our current conceptual framework. This research is novel for healthcare. Whilst focussing on innovation capacity/capability, the principles may apply more widely, including to research. Highlighting and addressing this knowledge gap could help oncology teams improve: a) the quality and sustainability of clinical care, delivering agile clinical services now and for the future; b) cancer innovation/research capacity, capability, quality; and c) the wellbeing and engagement of clinical staff. Greater value from research/innovation could be delivered through maximising the positive relationship between innovation and wellbeing whilst avoiding negative interactions.

Funder acknowledgement: NA

Theme 6, Abstract 9

Abstract Contents

Inclusion in cancer prehabilitation: Qualitative research to explore access and adherence to cancer prehabilitation in Wales

Alexandra Mitchell1, Manasi Patil1, Sherina Lowe1, Akhilesh Ramachandran1, Tessa Watts1, Jane Hopkinson1,2

1. School of Healthcare Sciences, Cardiff University

2. On behalf of the NIHR I-Prehab Project research team

Background

Prehabilitation for patients awaiting cancer treatments comprises education and/or interventions for physical activity, nutrition and emotional wellbeing by a multidisciplinary team. Prehabilitation may lead to faster recovery times and improved oncological outcomes. However, people from some minority ethnic groups and socioeconomically deprived communities are under-represented in cancer prehabilitation.

Aim

Identify barriers and enablers of access and adherence to cancer prehabilitation.

Methods

NHS services in Wales delivering prehabilitation for adults with upper gastrointestinal, colorectal, lung, prostate, or breast cancer were included. Qualitative data were collected between November 2023 and September 2024 from seven NHS services through observations of prehabilitation consultations (20 per site, 6 sites), brief interviews with healthcare professionals (HCPs), semi-structured interviews with patients and family carers (6 per site, 6 sites), and focus groups with HCPs (one per site, 7 sites). Thematic framework analysis of qualitative data was conducted using an adapted version of the World Health Organisation adherence framework.

Results

Enablers of engagement with cancer prehabilitation include understanding of and confidence in prehabilitation, trust in healthcare professionals, social support, tailoring of prehabilitation advice i.e. adapted to individual ability, co-morbidities, lifestyle, and proximity of prehabilitation service. Barriers include misalignment of patient and provider expectations, overload and overwhelm of information and appointments associated with cancer diagnosis, and inability to prioritise prehabilitation due to other commitments, physical or mental health symptoms, or lack of transport.

Conclusion

NHS Providers should work to optimise enablers and overcome barriers identified in this research to reduce inequalities in access and adherence to cancer prehab.

Funder acknowledgement: National Institute for Health and Care Research

Theme 6, Abstract 10

Abstract Contents

Understanding the barriers and facilitators affecting the use of remote consultations among marginalised communities: a mixed-methods systematic review

Julia Hiscock1, Grace McCutchan2, Kate Brain2, Richard Neal3

1. North Wales Centre for Primary Care Research, Bangor University

2. Cardiff University

3. University of Exeter

Background

Remote consultations are viewed as a potential tool to address increased demand from patients in primary care and pressure on the NHS workforce, although the evidence suggests they may create new and exacerbate existing inequalities. Marginalised groups face inequalities in both primary care and cancer diagnosis, but it remains unclear how they experience remote consultations when accessing primary care for suspected cancer symptoms. The aim of this study is to conduct a mixed-methods systematic review to understand the factors affecting the use of remote consulting among marginalised groups.

Methods

This mixed methods systematic review will be conducted using a convergent integrated approach, combining quantitative and qualitative data. Searches of peer-reviewed literature will be undertaken in Medline (via Ovid), Embase, PsychINFO (via ProQuest) and CINAHL (via EBSCOhost). Data extracted will include specific details about the study population and participant characteristics, how the authors defined and measured their study population, methods, setting, the format of remote consultation and patient symptoms. Quantitative data will be transformed into textual descriptions, following which all data will undergo narrative synthesis and be analysed thematically.

Results

This study will result in a deeper understanding of the barriers to and facilitators of remote consulting among marginalised populations. This will feed into the next phase of the study, which will consist of interviews with marginalised groups and focus groups with general practice teams across Wales and Northwest England. Ultimately, the aim is to develop a set of guidelines or an intervention to improve remote consultations for marginalised groups.

Funder acknowledgement: Joint funders - North West Cancer Research and Tenovus Cancer Care

Theme 6, Abstract 11

Abstract Contents

Could we utilise ‘one stop shop’ clinics to help ensure our cancer patients meet endoscopy waiting targets?

Jennifer Waterman1, Michael Beddard2, Heuy Yi Chong2

1. University Hospital of Wales, Cardiff and Vale University Health Board

2. Centre for Healthcare Evaluation, Device Assessment and Research (CEDAR), Cardiff and Vale University Health Board

Introduction

With diagnostic endoscopy waiting lists exceeding 25,000 in Wales in 2024, alternative solutions are urgently needed to ensure urgent suspected cancer (USC) referrals meet waiting time targets. Single use endoscopy (SUE) could offer a practical solution to this challenge. By utilising SUE in one stop shop (OSS) colorectal clinics for low-risk patients could allow endoscopy departments to focus resources on USC endoscopies.

Our aim was to assess the potential impact and feasibility of using SUEs in a OSS clinic by analysing data from flexible sigmoidoscopies (FS) performed within a single health board.

Methods

A retrospective analysis of Welsh Clinical Portal was conducted on all FS performed in a single Welsh health board over 1 month (January 2023).

Results

In January 2023, 163 patients underwent a FS. Average age was 55.2 years with 45% Male and 55% Female. FS referrals included 45% USC, 44% urgent, 10% routine and 1% for surveillance. The most common reason for referral was for rectal bleeding (42%). 85% (n=138) patients had either no sedation or Entonox. 88% (n=143) had a phosphate enema for bowel preparation and only 3 patients had to have a further FS due to poor bowel preparation.

Discussion

79% of patients undergoing a FS in the endoscopy department did not require intravenous sedation or oral bowel preparation – key factors supporting the feasibility of implementing SUE in a OSS clinic. The adoption of SUE could redirect low-risk patients to OSS clinics rather than endoscopy waiting lists, offering a practical solution to address rising endoscopy demands.

Funder acknowledgement: Cardiff Capital Region Challenge Fund

Theme 6, Abstract 12

Abstract Contents

CRT Together Improving the Cancer Journey programme: 1-year evaluation findings of a referral service addressing the non-clinical needs of people affected by cancer

Ann Broadway1, Alice Timbrell2

1. Coalfields Regeneration Trust

2. Urban Foresight

Coalfields Regeneration Trust, in partnership with Macmillan Cancer Support, are delivering a 5-year programme supporting people affected by cancer (PABC) with their non-clinical needs. Community-based Link Workers provide referrals to community support services. The programme aims to improve the cancer experience for people living in former Coalfields communities. It is being implemented in Cwm Taf Morgannwg University Health Board, in areas experiencing high levels of deprivation, health inequalities and cancer rates. Programme stakeholders include the Health Board, clinical healthcare teams and local voluntary sector organisations Here, we discuss the one-year evaluation findings from the development and early implementation of the programme. Evaluation methods include interviews with Link Workers and voluntary organisations supporting PABC, and observations of project meetings. Following initial scoping and development, the programme officially launched in March 2024. As of 31st October 2024, 129 people were supported and 256 referrals made. Learnings from early implementation include the value of involving people with lived experience, the need for clear, targeted communications to maintain effective stakeholder relationships, and the importance of flexible programme management to adapt to challenges, learnings and successes. To strengthen the reach of the programme, the project team are working to expand both health and community referral pathways. Current findings show promise for the CRT Together programme. There is a steady influx of participants, who highlight the positive impact of the programme, bringing them peace of mind and connecting them to practical support. However, further efforts are needed to embed the service and ensure programme effectiveness.

Funder acknowledgement: Macmillan Cancer Support

Theme 6, Abstract 13

Emergency Cancer Diagnoses - Impact on Healthcare Staff: Initial Analysis

Karen Wingfield1,2 , Dr Sarah Fry3, Emeritus Professor Daniel Kelly4

1. PhD Student School of Healthcare Sciences, Cardiff University

2. Macmillan Acute Oncology CNS, Cwm Taf Morgannwg UHB

3. School of Healthcare Sciences, Cardiff University

4. Emeritus Professor, School of Healthcare Sciences, Cardiff University

Introduction

Abstract Contents

Across the NHS in Wales the number of people receiving a cancer diagnosis in emergency settings is rising. The impact of this on clinical staff is poorly understood. This ongoing study focuses on the experiences of clinicians involved with these patients in District General Hospitals (DGH). Specifically, it aims to develop an indepth understanding of clinicians’ experiences of working with patients diagnosed with cancer in emergency settings to inform and contribute to the future development of Acute Oncology Services and the emergency diagnostic cancer pathway.

Methodology

Qualitative, narrative methodology was adopted using semi-structured individual interviews with 13 purposively recruited participants from two University Health Boards with emergency and acute admissions services and known to provide emergency cancer diagnoses. Data were collected between March-August 2024, transcribed verbatim and analysed using a narrative thematic approach.

Results

Preliminary narrative analysis has generated four core themes:

• Preparing for a serious conversation.

• Passing the baton.

• Learning to manage myself.

• How can I do this better?

Clinicians prepared themselves mentally, physically, and logistically to break bad news. Clinicians’ involvement with a patient from diagnosis in the emergency setting helped develop rapport, which was perceived as being helpful to the clinicians at a later stage. Clinicians were keen for communication training about breaking bad news in the emergency setting. For some clinicians a ‘follow up watch list’ was perceived to be helpful.

Ongoing analysis will build on the themes to provide recommendations for clinical practice, education, policy and research.

Funder acknowledgement: HEIW

Theme6,Abstract14

AbstractContents

Theme 6, Abstract 15

Abstract Contents

How might the provision of smoking cessation services be adapted to improve uptake and success for people in low socioeconomic groups? A qualitative study (PROCESS Study)

Dr Pamela Smith, PhD1 , Lucia Dahlby, MScR2, Dr Evgeniya Plotnikova, PhD2, Dr Rebecca-Bell Williams, PhD3, Rebecca Thorley3, Dr Fiona Dobbie, PhD2, Dr Tessa Langley, PhD3, Dr Ilze Bogdanovica, PhD3, Prof Kate Brain, PhD1 , Prof Rachael Murray, PhD3, Dr Leah Jayes, PhD4

1. Cardiff University, Wales

2. University of Edinburgh, Scotland

3. The University of Nottingham, England

4. Nottingham Trent University, England

Background

Smoking is a key driver of health inequalities and a leading cause of cancer incidence. Stop Smoking Services (SSS) offer a combination of behavioural and pharmacological support. Individuals who use SSS are three times more likely to successfully quit than those who try to quit unaided, but uptake of services is low, particularly amongst people from low socioeconomic (LSE) backgrounds. The aim of this study was to understand the barriers and facilitators to accessing SSS in this population.

Methods

Qualitative interviews with SSS providers (n=22) and potential or current service users from LSE backgrounds (n=115) across the UK. Interviews were coded thematically and analysed using the COM-B model which cites Capability (C), Opportunity (O), and Motivation (M) as factors for changing behaviour (B).

Findings

Facilitators to accessing SSS included proximity of services, flexibility of service delivery, and free NRT provision. Barriers included waiting lists, staffing shortages, lack of service visibility and advertisement, perceived stigma and lifestyle factors. Recommendations for service enhancement included improved visibility and awareness of SSS (Capability), enhanced community links to embed services or support referral pathways (Opportunity) and person-centred approaches to SSS delivery (Motivation).

Conclusion

Findings provide evidence on practical solutions for adapting SSS delivery, with potential to increase equitable uptake and improve outcomes. Removing structural barriers through tailored support and targeted promotion of local SSS is essential to maximise service uptake. The use of community outreach services was identified as an important way of maximising targeted work to improve access to SSS in LSE settings.

Funder acknowledgement: Cancer Research UK

Theme 6, Abstract 16

Using a behavioural science approach to raise awareness of breast screening. Naomi Morgan1, Charlotte Cullum1, Rhian Meaden1

1. Cwm Taf Morgannwg University Health Board

Introduction

Abstract Contents

Female breast cancer is the second most common cancer in Wales. Breast screening looks for breast cancer before symptoms show. Finding breast cancer early gives the best chance of successful treatment and survival. Therefore it is important to ensure eligible women make an informed decision about attending their screening appointment.

Aim

To plan, deliver and evaluate a behaviourally informed breast screening social media campaign.

Methodology

A behaviourally informed social media campaign that focused on key breast screening messages and identified target behaviours was developed with Public Health Wales, and shared with the public. A mixedmethods survey was additionally used to further capture localised barriers and facilitators to breast screening for inclusion in future campaigns/targeted interventions. Survey questions were informed by a rapid review of barriers and facilitators to cancer screening uptake in under-served populations.

Results

Survey findings highlighted commonly reported facilitators and barriers to attending breast screening. Commonly selected facilitators include understanding the importance of attending breast screening and the invite letter being easy to understand.

Conclusion

The project provided useful learning on using a behaviourally informed approach to support breast screening uptake. Findings enabled colleagues and partners to gain a greater understanding of the facilitators and barriers to attending breast screening for women in local communities. Following the project, a partnership approach document was developed to detail recommendations and best practice in raising awareness of breast screening.

Funder acknowledgement: NA

Theme 6, Abstract 17

Abstract Contents

Preparing the public for equitable and informed implementation of Multi-Cancer Early Detection (MCED) blood tests

Delyth Price1, Richard Adams2, Kate Brain1, Julie Hepburn3, Rashmi Kumar3, Laura Marlow4, Uju Ogbonna1, Fiona Wood1, Harriet QuinnScoggins1

1. Division of Population Medicine, Cardiff University

2. Centre for Trials Research, Cardiff University

3. Lay Representative

4. Centre for Cancer Prevention, Screening and Early Diagnosis, Queen Mary University of London

Background

Multi-Cancer Early Detection blood tests (MCEDs; tests to look for cancer-related signals in the blood) could potentially advance cancer diagnosis, pending further evidence of clinical utility and consideration of diagnostic infrastructures. However, evidence about the information and communication needs of the public, particularly under-represented groups, regarding these tests is lacking. Developing person-centred communication strategies will be critical to ensure that this new technology does not increase existing cancer inequalities if implemented.

Aim

To understand the information and communication needs of diverse members of the public for MCED blood tests in symptomatic and screening contexts, with a focus on health equity.

Methods

Focus groups with members of the public. Participants were recruited via a specialist recruitment agency and purposively sampled to include a range of ethnicities, socioeconomic status, and from all four UK nations.

Results

Eight focus groups were conducted with 47 members of the public from England (n=36), Scotland (n=5), Wales (n=4) and Northern Ireland (n=2). Participants included 23 women and 24 men from Black, White European and South Asian ethnicities, with an average age of 49 (range: 27 to 73 years). Levels of socio-economic deprivation, health literacy, previous engagement in cancer screening and experience with cancer diagnoses varied. Data are being transcribed for thematic analysis and mapping to the Socioecological Model. Preliminary results will be presented.

Implications

Outputs will support a platform for future research to develop and evaluate targeted interventions supporting equitable and informed uptake and delivery of MCED blood tests for diverse populations.

Funder acknowledgement: Cancer Research UK

Royal College of Radiologists continued personal development (CPD) credits

Conference learning objectives

Gain an understanding of cancer research taking place across Wales and how it fits with the six

All-Wales cancer research strategy (CReSt) priority themes

Understand the pros and cons of immunotherapy as cancer treatment from multiple clinical and non-clinical perspectives

Achieve a greater understanding of Wales' spinout companies and the research that led to their conception

Learn about a patient's experience of being part of research, and the value that public and patient involvement adds to cancer research

Attendance at the Wales Cancer Research Conference 2025 provides the following CPD credits in accordance with the CPD Scheme of the Royal College of Radiologists:

Conference attendance: 7 credits (whole day)

Oral abstract presentation: 5 credits for first author, 1 credit for other authors

Poster presentation: 3 credits for first author, 1 credit for other authors

If you require a certificate of attendance in order to log your credits, please email wcrc@cardiff.ac.uk after the conference providing your GMC number where possible.

Please do not share or reproduce abstract, poster or presentation content from this event; please treat data presented as confidential.

Peidiwch â rhannu nac atgynhyrchu cynnwys crynodeb, poster na chyflwyniad o'r digwyddiad hwn; dylech drin data a gyflwynir yn gyfrinachol.