2021 Annual Report - University of Chicago Medicine Comprehensive Cancer Center

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2021 Annual Report

Director’s Message

In March 2021, nationally recognized physician-scientist Kunle Odunsi, MD, PhD, became the Cancer Center’s new director.

Welcome to the 2021 Annual Report, in which we will share the progress of the University of Chicago Medicine Comprehensive Cancer Center’s efforts to advance cancer research over the course of a year. I feel an immense sense of pride in what we have accomplished together in 2021 in spite of an unrelenting pandemic. In my new leadership role, I have spent time talking with our researchers and physicians, and one thing I see is a steadfastness in their commitment to always strive for excellence. It quickly became clear that UChicago is a special place where curious minds bring their expertise to bear on the most challenging problems. Although we’ve been humbled by the pandemic and have uncovered uncomfortable truths related to our culture as a nation, we have advanced our research mission and provided hope and healing to many. I am excited and honored to carry on the work of immediate past director, Michelle M. Le Beau, PhD, to bolster the impact of UChicago Medicine as a world-class destination for cancer research and care. Thank you to our supporters, patients, caregivers and community members for giving us a reason to make a world without cancer a reality.

Kunle Odunsi, MD, PhD Director, University of Chicago Medicine Comprehensive Cancer Center Dean for Oncology, Biological Sciences Division The AbbVie Foundation Distinguished Service Professor of Obstetrics and Gynecology

200+ 1,758 424 physicians and scientists engaged in cancer research

volunteers enrolled on clinical trials

publications in peer-reviewed journals

8M+

11

$56M+

3.3

1

petabytes of data in national Genomic Data Commons hosted at UChicago

National Cancer Institute-designated Cancer Centers in Illinois

UChicago Medicine doctors on Chicago magazine’s 2021 “Top Doctors” list

$9M

50 yrs

16 yrs

population of area served

grant from the National Cancer Institute to improve treatments for ovarian cancer

locations across Chicagoland serving cancer patients close to home

of only

2

since President Nixon waged war on cancer with the National Cancer Act

total in peer-reviewed cancer research grants awarded to members

175

nationally ranked as a best hospital for cancer by U.S. News & World Report

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2021 Annual Report

2021 Snapshot

Spotlight Natalie Ford

Natalie Ford created an endowment fund to support scientific research, education and training for breast cancer at the University of Chicago in memory of three women close to her who were affected by the disease. (courtesy: Nancy Wong)

Community member’s dedication to helping others leads to gift supporting cancer research Natalie Ford, a resident of Chicago’s South Side, is committed to helping others, a value she learned at an early age from her mother.

“My mother was a strong woman who led by example,” Ford said. “She always said, ‘Life isn’t about what you can do for yourself; it’s about what you can do to help society.’”

Carrying forward her mother’s legacy, Ford has created an endowment fund with a gift of $100,000 to support scientific research, education and training for breast cancer at the University of Chicago. The fund was created in memory of three women close to her who were affected by the disease.

Ford, who works for a nonprofit organization that helps with job training and placement, was able to make the gift by building on her inheritance from family members through personal investments and disciplined savings. She notes that, regardless of the amount, gifts made by people like her who have supported family and friends affected by cancer can add up and make a difference.

“The fund I’ve established represents my dedication and care for those who come behind me,” Ford said. “There are a lot of problems in the world today, and while I can’t solve everything, I have found a way to focus on what’s most important to me to have the greatest impact. I think if you look beyond yourself, you begin to see the world through a new lens and recognize the importance of helping others.”

Ford hopes the fund she established will not only honor the memory of the three women it is named for, but will also lead to better treatment options for breast cancer and, ultimately, a cure. She also hopes the gift can help provide supportive services for patients and their family members.

“When you first hear that a family member has been diagnosed with cancer, it can be isolating, and you can experience a range of emotions — anger, sadness, helplessness,” Ford said. “I’m hoping that this funding can help provide support because not everyone has a nuclear family, not everyone has someone they can call when they’re facing something like this.”

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University of Chicago Medicine Comprehensive Cancer Center

A COMMUNITY THAT’S RELENTLESS

2021 Annual Report

Community

Connecting with the community for health equity CommunityAcademic Mini Grants

The Office of Community Engagement and Cancer Health Equity (OCECHE) established a $25,000 community-academic research partnership mini-grant program to build relationships and develop strong community-academic partnerships between five member organizations of OCECHE’s Community Advisory Board and four University of Chicago Medicine cancer researchers to drive community-engaged cancer research projects across the full cancer research spectrum.

The relationship-development grants are for joint projects over a 6-month period to bring community perspectives into the cancer research process.

COMMUNITY PARTNER

ACADEMIC RESEARCHER(S)

EGFR Resisters Lung Cancer Patient Group

Marina Garassino, MD

The Cancer Support Center

Greg Karczmar, PhD

Equal Hope

Yasmin Hasan, MD

Screen to Succeed

Adam DuVall, MD, MPH, and Wendy Stock, MD

Blue Hat Foundation

Anthony Williams, PhD

CORE Program

The Community Outreach Research Engagement (CORE) program is a National Cancer Institute-funded educational infrastructure to build capacity and promote bidirectional engagement between community members and UChicago basic and translational scientists. The CORE program helps community advocates learn scientific principles and research advocacy and teaches researchers effective community engagement and scientific communication skills. The curriculum includes University of Chicago and community presenters, as well as research advocacy training from the Oregon Health & Science University Knight Cancer Institute and science communication training from the Stony Brook University Alan Alda Center for Communicating Science. We have 33 CORE members across the two cohorts that work in parallel and collaboration. Their efforts will be showcased in a communityacademic research summit in 2022.

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University of Chicago Medicine Comprehensive Cancer Center

HealthyU, a program that started as a cancer screening and education initiative to reach hospital employees, has expanded to a virtual format to include community members. HealthyU consists of weekly webinars featuring UChicago faculty and community experts on a variety of cancer-focused content. To date, we have had over 40 faculty members and 25 community members share their knowledge with over 400 participants on 65 different webinars. The webinar series gets overwhelmingly positive reviews, with >99.5% of participants reporting that the speakers were knowledgeable and delivered information in a clear and engaging manner. In addition, we have created virtual cancer screening pledge cards, online toolkits to provide cancer education materials and contests to engage with the community about cancer education.

HealthyU

OCECHE was awarded a grant from ESPN to promote Black participation in cancer clinical trials. Through this grant, we have expanded a Diversity in Clinical Trials workgroup made up of OCECHE Community Advisory Board members, cancer survivors and patient advocates to identify barriers and facilitators to clinical trial participation in key community and clinical groups. Through this workgroup, we are creating a multimodal online community toolkit to provide education and dispel myths about clinical trials.

Empowered-U

LUCERO, Latinos United for Cancer Education, Research and Outreach, our Latinx cancer control task force, works to engage the Latinx communities within our catchment area and works to meet Latinx-focused cancer needs. LUCERO includes representation from various Latinxserving community-based organizations, UChicago Medicine clinicians, cancer investigators and staff members from the Center for Supportive Oncology. LUCERO has administered a needs assessment to Chicagoland Latinx communities to understand their cancer-related priorities, barriers, needs and strengths. Using this data, LUCERO will identify key areas to focus their outreach work within local Latinx communities.

LUCERO

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2021 Annual Report

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Spotlight Bonnie Rothman

Top right Bonnie Rothman’s mother (left), Nancy W. Fry Bottom right Bonnie Rothman’s grandmother, Mary C. Landis

Gift propels research to advance understanding of pancreatic cancer Pancreatic cancer touched Bonnie Rothman’s life twice. First, her maternal grandmother was stricken with the disease and passed away soon after. More than 30 years later, Rothman’s mother was diagnosed and passed away three-and-a-half months later.

“I don’t think any disease should have the impact of a train wreck, especially in this day and age with the amount of knowledge we have in cancer,” Rothman said.

After losing her mother and grandmother, Rothman felt frustrated by the limited treatment options available and committed herself to doing what she could to help advance understanding of the disease.

Seeking to improve diagnosis and prevention of pancreatic cancer, Rothman made a $100,000 gift supporting the Pancreatic Cancer Early Detection Program within the Gastrointestinal Cancer Risk and Prevention Clinic at UChicago Medicine. The gift will enable clinic director Sonia Kupfer, MD, associate professor of medicine, and her team to expand the clinic’s efforts to advance research studies aimed at finding innovative and less invasive ways to detect pancreatic cancers earlier.

“Bonnie’s gift will help us build the inf ra structure to identify new biomarkers and develop new genetic tests to catch these cancers earlier,” Kupfer said . “ Without philanthropic support from donors like Bonnie, we wouldn’t have the resources to get this important work off the ground.”

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University of Chicago Medicine Comprehensive Cancer Center

PATIENT CARE THAT’S RELENTLESS

2021 Annual Report

Patient Care

A follow-up CT scan for a patient treated for prostate cancer showed a normal-appearing, 2 mm lymph node (top image).

But a PSMA PET scan spotted prostate cancer cells in the tiny node (see arrow in bottom image).

Seeing prostate cancer in a new way

For years, one of the most powerful molecular imaging tools, positron emission tomography (PET), has frustrated doctors when it comes to detecting prostate cancer cells. Until recently, the available radiotracers — the radioactive molecules doctors use to show cancer cells on PET scans — did not routinely bind to this specific type of cancer.

Now, however, a new radiotracer is capable of precisely and reliably tagging prostate cancer cells anywhere in the body. In 2021, UChicago Medicine was one of the first institutions in Chicago to offer the PSMA PET scan and the only institution in the city to have participated in the CONDOR and OSPREY clinical trials that helped piflufolastat F 18, also known as Pylarify®, gain FDA approval.

Piflufolastat is administered to patients with an IV. Radioactive molecules bind to prostate-specific membrane antigen (PSMA), a protein found on the surface of prostate cancer cells. The radiotracers are detected by the PET machine, which displays on a scan where they have settled on prostate cancer cells in the body.

Piflufolastat cannot tag every single prostate cancer cell, but it far surpasses the level of detection previously available with CT, MRI or bone scans. The improvement in diagnostic precision offered by PSMA PET could affect the treatment decisions of many patients.

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University of Chicago Medicine Comprehensive Cancer Center

UChicago Medicine is the first program in Chicago to offer Abecma™, a cell-based gene therapy for patients with treatment-resistant multiple myeloma. In March 2021, the FDA approved Abecma as the first cell-based gene therapy for patients with treatment-resistant multiple myeloma. It works by specifically targeting the BCMA receptor on the surface of myeloma cells. Patients with triple-refractory multiple myeloma who have already undergone four or more therapies, including anti-CD38 monoclonal antibody, a proteasome inhibitor and an immunomodulatory drug, are eligible and should discuss the treatment with their doctor.

New cellular therapy offers hope for patients with multiple myeloma

UChicago Medicine was chosen as the first hospital in Chicago to offer Abecma because of its expertise in cellular therapy and strong program for treating multiple myeloma, which includes a multidisciplinary clinic devoted to fast-tracking care for new patients. UChicago Medicine is a member of the Multiple Myeloma Research Consortium, an association of 25 academic hospitals dedicated to bringing promising therapies to patients.

In 2021, UChicago Medicine created the High-Risk Lymphoma Clinic to meet the unique needs of patients with aggressive lymphomas. A team of highly skilled specialists comprising physicians from medical oncology, radiation oncology, hematopathology and radiology work together to provide prompt, focused care. Lymphoma nurse navigators are on hand to support patients and their families throughout the cancer journey. The clinic offers the full spectrum of treatments for aggressive lymphoma, including advanced chemotherapies, radiation therapy, stem cell transplantation, immunotherapy, CAR T-cell therapy and clinical trials investigating promising new treatments.

Clinic specializes in expert care for aggressive lymphomas

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2021 Annual Report

Spotlight The Hooglands

Family’s $5M gift advances UChicago Medicine’s vision for cancer immunotherapy Since its inception, the Hoogland family’s corporate “Round It Up for Lymphoma” campaign has raised more than $4 million for the research of Sonali Smith, MD, director of UChicago Medicine’s Lymphoma Program, allowing her to launch the Hoogland Lymphoma Biobank in 2013. Smith has since collected more than 1,000 blood samples and nearly 500 tissue samples — which are used to help researchers better understand the disease — from nearly 1,500 patients.

Keith and Susan Hoogland

Building on the success of the biobank, the Hooglands began thinking about how they could support research on other cancer types to have an even greater impact. Their ambition inspired Smith to introduce them to Thomas Gajewski, MD, PhD, the AbbVie Foundation Professor of Cancer Immunotherapy, and one of the world’s leading experts in his field.

Gajewski and his colleagues have an ambitious goal: double the immunotherapy response rate in 10 years or less. His vision inspired the Hooglands to pledge $5 million toward accelerating cancer immunotherapy research at UChicago Medicine so that more patients can benefit from the life-saving therapies.

“I’m a problem solver and that’s one of the things that connected me to Dr. Smith and Dr. Gajewski,” Keith said. “There is a long-term goal: solve lymphoma or — through immunotherapy — solve the riddle of cancer.

I think of it as an investment in something that has a good chance of working or will lead to something — some big breakthroughs.”

By focusing research on the patients for whom immunotherapies fail, Gajewski aims to identify, understand and overcome the defenses that cancers use to escape or withstand immune attack. Over the past few years, his team has been collecting tumor, tissue, blood and stool samples from hundreds of patients participating in immunotherapy clinical trials.

These banked samples represent a gold mine of data for understanding what helps one patient’s response and what hinders another’s.

The Hoogland’s generous gift will help Gajewski identify those reasons so that more cancer patients can benefit from all that immunotherapy has to offer. “Philanthropy fills in the gaps,” he said. “It allows researchers to take risks and tackle the big ideas. Keith and Susan’s generosity will have a profound impact on our understanding of immunotherapy response and ability to develop treatments that help the most patients.”

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University of Chicago Medicine Comprehensive Cancer Center

RESEARCH THAT’S RELENTLESS

2021 Annual Report

Research

Tackling bias in AI to deliver the promise of personalized cancer treatment Alexander Pearson, MD, PhD (courtesy: Jimmy Fishbein)

Artificial intelligence (AI) tools have the potential to diagnose cancer subtypes, and even molecular signatures, simply from looking at tumor sections under the microscope. The promise of AI and deep learning could help clinicians gain vital information to make personalized treatment plans from patient biopsies; however, despite this promise, new research shows these algorithms can lead to biased predictions.

Senior authors Alexander Pearson, MD, PhD, assistant professor of medicine, and Robert Grossman, PhD, Frederick H. Rawson Distinguished Service Professor of Medicine, identified clear bias in deep learning analyses of large biorepositories of digital histology samples.

Although the purpose of AI analysis is to find biological features of the cancer tissue, Pearson and Grossman found that a widely utilized algorithm was grouping patient samples by where they were processed, leading to inaccurate conclusions about patients based on where they lived. In order to improve relevant predictions of biological factors, such as tumor genetics and patient outcomes, they proposed approaches to improve the current methodology.

AI algorithms that analyze tumor tissue are built on established methods of diagnosing disease. This begins with a biopsy, a small sample that is taken from a tumor for analysis. The sample is prepared on a slide and observed through a microcope. For modern AI techniques, highresolution digital images of the tissue slices are captured and added to a library of other images. AI algorithms “learn” from inputting large numbers of biopsy slides. Through this approach, AI is able to find biological signatures within the slides that can inform clinicians about biological details of the tumor not visible to the eye.

The research team analyzed the output of deep learning models trained on a large national biorepository of cancer data, and found that the signatures generated by the AI algorithm were based on artifacts connected to where patients were diagnosed, rather that biological factors. This means that a patient could receive a diagnosis, and even treatment recommendations, based on where they live rather than on biological factors within their cancer.

The authors concluded that this type of bias is avoidable if the training data for algorithms is modified by equally distributed outcomes, or by isolating sites of diagnosis. These changes could produce accurate tools based on biology that would provide information to correctly diagnose patients and optimize their treatment plans.

Howard et al., Nature Communications 12:1-13, 2021

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University of Chicago Medicine Comprehensive Cancer Center

Immunotherapy has become a standard treatment across many cancer types, but little is known about the immune response to tumors in pediatric patients and how it differs from adults. For treating neuroblastoma, a pediatric cancer that starts in nerve cells and is most commonly diagnosed in infants and young children, it is critical to understand the potential benefits of powerful anti-cancer treatments.

This study showed that children treated for high-risk neuroblastoma had better survival if their tumors were T cell-inflamed — meaning that a large number of T cells are present — and high in neoantigens, cancer-specific markers that allow tumors to be recognized by T cells.

Improving options for children with neuroblastoma

Ami Desai, MD, assistant professor of pediatrics, led a team that aimed to find out how the immune systems of children with neuroblastoma respond to tumors. Their goal was to achieve a deeper understanding of the immune mechanisms in neuroblastoma tumors to provide insight for the development of new immunotherapies for these pediatric patients.

Their approach was to examine hundreds of past cases of childhood neuroblastoma. They performed a genetic analysis of each tumor to gather information about the immune response in each patient, including the immune cell population in the tumor and how the immune cells were responding. Their results uncovered dramatically different immune profiles in tumors from different patients and showed that a strong immune response was tied to increased survival from neuroblastoma.

The team found that patients with tumors with high levels of cytotoxic T cells — the immune cells known for their ability to kill tumor cells — were more likely to survive. A deeper analysis showed that tumors varied in their number of neoantigens, and patients with tumors high in neoantigens were more likely to survive.

Findings from this study may lead to new approaches to improve treatment options for children with relapsed or difficult-to-treat neuroblastoma. The correlation of improved survival of children with certain immune markers supports a role for an immunotherapeutic course of action for treatment of neuroblastoma.

Bao et al., Journal for Immunotherapy of Cancer 9:1-15, 2021

Pediatric cancer specialist Ami Desai, MD (courtesy: Jimmy Fishbein)

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2021 Annual Report

Research

Drivers of secondary cancers provide clues for treatment and prevention

For some patients that survive life-threatening cancers, there may be a risk of developing secondary cancers later in life that are associated with earlier chemotherapy treatment. These therapy-related myeloid neoplasms (t-MNs) are blood cancers that are difficult to treat. The genetic makeup of t-MN cells can provide clues about what is driving their development. A research team discovered that the loss of CUX1, a gene involved in regulating cell growth and division, played a major role in the initiation of these cancers and that restoring CUX1 function inhibited the development of t-MN. Megan McNerney, MD, PhD, associate professor of pathology, and her lab used a CUX1-deficient mouse model to determine the role of CUX1 in t-MN. They found that treatment with chemotherapy resulted in the development of t-MNs in mice without CUX1. Their experiments showed that CUX1 regulates what are known as DNA-damage response genes, which code for proteins that help to repair damaged DNA in cells. The results suggested that cells deficient in CUX1 will not be able to repair their DNA and could more easily become malignant.

Restoring CUX1 expression in myeloid cells prevented the development of cancer, revealing a potential novel approach — treatments that reinstate CUX1 expression.

The team observed that CUX1 levels decrease with age, which may be why older patients are more likely to develop some blood cancers.

More research is needed, but results from this study suggest that understanding the CUX1 status of patients may help to guide treatment decisions. If physicians know whether patients are CUX1-deficient, it could influence the decision to treat with chemotherapy.

As the number of cancer survivors increases, it’s expected that cases of t-MN will rise. These discoveries could help scientists develop new methods for treating patients with secondary cancers.

Imgruet et al., Blood 138:790-805, 2021

Megan McNerney, MD, PhD (courtesy: Jean Lachat)

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University of Chicago Medicine Comprehensive Cancer Center

2021 Annual Report

Many cancer immunotherapies rely on the activation of T cells, immune cells that can recognize specific markers on tumor cells and attack them, leading to cell death. Approaches to make use of other types of immune cells, such as innate immune cells, have not been as widely investigated. Unlocking the full potential of the immune system may be key in battling cancer.

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ELANE-mediated anti-cancer pathway

Learning how to tackle cancer from our own immune cells

Lev Becker, PhD, associate professor in the Ben May Department for Cancer Research, uncovered a mechanism that our innate immune cells use to battle cancer cells. Becker and his research team discovered that a factor from neutrophils, a protein called ELANE, has strong anti-cancer properties. ELANE was shown to activate cell death pathways specifically in cancer cells. This factor causes cancer cells to die in tumors and distant locations where they have spread, while sparing healthy cells.

Using human and mouse models, the team showed that ELANE attacks cancer cells by inducing DNA damage, inhibiting cell survival pathways and promoting production of reactive oxygen species, ultimately leading to the death of cancer cells. According to the researchers, ELANE was able to target many types of cancer cell lines. This ability suggests that the treatment may be able to work against many different types of cancer, including those that are notoriously difficult to treat, including triple-negative breast cancer, melanoma and lung cancer. Another potential benefit of ELANE is that it demonstrated a lack of side effects in mice, suggesting a potential for limited toxicity.

Immune cells of the mice were preserved as well, which boosted their anti-tumor immune response.

The researchers reported on a second protein that is released by neutrophils and is similar to ELANE, called PPE. PPE was demonstrated to induce a stronger therapeutic response than ELANE. Future studies are planned to find out how to maximize the therapeutic effects of ELANE/PPE, both as a single therapy and in combination with other cancer treatments.

Cui et al., Cell 12:3163-77, 2021 15

Research

Genetic mutations revealed that impact susceptibility to arsenicassociated cancers Habibul Ahsan, MD (courtesy: Serena Mietus)

More than 200 million people worldwide are exposed to arsenic through drinking water and diet, increasing their risk for diseases, including skin, lung, bladder and kidney cancers. Recent publications from researchers at the Comprehensive Cancer Center have uncovered genetic and epigenetic susceptibilities to arsenic-associated cancers. These findings could lead to new approaches to prevent and treat these cancers.

In most people, a protein called AS3MT helps to break down arsenic and eliminate it from the body. Investigators Brandon Pierce, PhD, associate professor of public health sciences, and Habibul Ahsan, MD, Louis Block Distinguished Service Professor of Public Health Sciences, Medicine and Human Genetics, sought to determine the impact of rare protein-coding variations in the AS3MT gene on arsenic metabolism across multiple populations.

The cohorts included were the Health Effects of Arsenic Longitudinal Study (HEALS) from Bangladesh, the Strong Heart Study (SHS) of Native Americans and the New Hampshire Skin Cancer Study (NHSCS).

They analyzed genetic sequences of AS3MT and arsenic-derived molecules in the urine of all participants. Rare genetic mutants of AS3MT were discovered in all groups, and were associated with decreased levels of arsenic byproducts in the urine, indicating these mutations impair the breakdown of arsenic. These variants likely resulted in increased retention of arsenic and associated health effects of arsenic toxicity, including increased cancer risk.

Delgado et al., Environmental Health Perspectives 129:59003, 2021

In a separate study, Yu-Ying He, PhD, professor of medicine, and collaborators showed that chronic arsenic exposure leads to decreases in epitranscriptomic modification of cellular RNAs — changes to RNA molecules that don’t impact their sequence. Specifically, continuous exposure to low levels of arsenic increased a protein called FTO, which decreased m6A RNA methylation, a type of epitranscriptomic modification. These changes led to increased development of skin tumors in a mouse model. These findings suggest that targeting FTO and m6A RNA methylation may be key to preventing or treating arsenic-induced skin cancer.

Overall, these findings uncovered mechanisms of arsenic-induced cancer susceptibility that could be targeted for prevention and treatment of these cancers.

Cui et al., Nature Communications 12:2183, 2021

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University of Chicago Medicine Comprehensive Cancer Center

For many types of cancer, lethality is caused by the spread of the cancer cells throughout the body — or metastasis. Previous attempts to block metastasis have not been fully effective because cancer cells are heterogeneous, allowing some cells to survive and continue to spread.

A study reported a new approach to defeating metastasis may be a low-dose, four-drug combination that prevented the spread of cancer in mice without triggering drug resistance or recurrence.

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2021 Annual Report

Blocking the ability of cancer cells to spread

Co-senior author Marsha Rosner, PhD, the Charles B. Huggins Professor at the Ben May Department for Cancer Research, and collaborators analyzed gene expression data from patients participating in the Cancer Genome Atlas study to understand how a metastasis-suppressing protein called RKIP functions in cancer cells. They found that RKIP inhibits the expression of a network of genes that promote metastasis.

The research team then created a four-drug combination to copy how RKIP suppresses the ability of cancer cells to spread. They administered the treatment to mouse models of metastatic breast cancer and found that it blocked metastasis and increased survival of the mice.

Importantly, the drug combination blocked the spread of cancer cells without triggering drug resistance.

Modeling the targeted gene expression networks allowed the researchers to create a map of the connections between the various signaling pathways and helped to explain why the drug combination was effective.

Finally, the team identified patients with breast cancer in the Cancer Genome Atlas who may potentially benefit from the treatment based on the gene expression patterns of their cancer.

Overall, the findings suggested a new approach to preventing cancer metastasis in patients by simultaneously targeting multiple pathways within a metastasis-promoting network, and may also help identify patients who may benefit from this treatment approach.

Yesilkanal et al., eLife 10:1-40, 2021

Marsha Rosner, PhD, (right) and Nykia Walker, PhD (courtesy: Jimmy Fishbein)

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Research

State-of-the-art technology assists the development of novel breast cancer treatment Geoffrey Greene, MD, PhD (courtesy: Jimmy Fishbein)

The majority of breast cancers are estrogen receptor positive, or ERpositive. This means that the cancer cells grow in response to the hormone estrogen. Postmenopausal patients are often treated with drugs called aromatase inhibitors that suppress estrogen production.

Patients with breast cancers that become resistant to this treatment are usually switched to the drug fulvestrant, which blocks the estrogen receptor. New research shows that a drug called lasofoxifene may outperform fulvestrant in preventing tumor growth and spread, and offer reduced side effects.

Senior author Geoffrey Greene, MD, PhD, Virginia and D. K. Ludwig Professor and Chair of the Ben May Department for Cancer Research, and his colleagues teamed up with collaborators from the Argonne National Laboratory to use the leading-edge resources of the Advanced Photon Source (APS) facility to optimize their search for improved breast cancer treatments. The APS uses ultrabright X-rays to visualize structures of proteins like estrogen receptors and their interactions with drug compounds. The APS confirmed that lasofoxifene binds to estrogen receptor molecules, which supports its activity as an estrogen receptor modulator.

To determine the effectiveness of lasofoxifene and test it against the standard therapy, researchers worked with mice that had ER-positive breast cancer tumors with activating ER mutations. They treated some of the mice with lasofoxifene and others with fulvestrant. They also tested both drugs in combination with palbociclib, a common chemotherapy drug that works by preventing cancer cells from multiplying.

The data showed that lasofoxifene was more effective than fulvestrant at preventing tumor growth and reducing metastasis. Combination therapies with palbociclib improved the effectiveness of both drugs, though the lasofoxifene/palbociclib combination was most effective.

Ongoing clinical trials are expected to provide additional data on the safety and effectiveness of lasofoxifene.

Lainé et al., Breast Cancer Research 23:1-12, 2021

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University of Chicago Medicine Comprehensive Cancer Center

Lymphatic vessels connect with lymph nodes throughout the body and play a critical role in the immune response, including anti-tumor immunity. Lymphangiogenesis, the growth of new lymphatic vessels, could help to traffic cancer antigens to lymph nodes and bring immune cells to a tumor, but could also have negative consequences of providing new paths for tumor cells to spread. Researchers have now developed an approach to take advantage of the potential anti-cancer benefits of lymphangiogenesis while preventing the spread of cancer cells.

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2021 Annual Report

Using lymphatic vessels to improve anti-melanoma immunity

Melody Swartz, PhD, William B. Ogden Professor in Molecular Engineering, previously discovered that lymphangiogenic tumors that make factors which promote the growth of lymphatic vessels are more responsive to immunotherapy. Unfortunately, these tumors were also more likely to spread through these budding lymphatic networks.

To exploit the potential benefit of new lymphatic vessel growth while overcoming the dangers, Swartz and her team developed a lymphangiogenic cell-based cancer vaccine. The vaccine, called VEGFC vax, is composed of cells that produce growth factors for lymphatic vessels.

When injected under the skin of a mouse at a site away from the tumor, the researchers found that lymphangiogenesis occurred at the site of injection. Consequently, transport of cancer antigens to lymph nodes increased, and high numbers of anti-tumor T cells formed. Another potential benefit was the recruitment of non-activated T cells into the injection site, leading to direct T-cell activation. The team showed that their vaccines initiated a broad T-cell response toward a range of melanoma antigens. A broad T-cell response to cancer cells is important because when there are numerous ways for T cells to recognize tumor cells, it makes it tougher for the tumor cells to disguise themselves.

Cell-based vaccines may seem surprising, but they have been used to battle various types of human cancers, including melanoma, prostate and pancreatic cancer. Some cell-based vaccines have been designed to produce other proteins that promote immune cell recruitment and activity, such as GVAX vaccines. These vaccines consist of genetically modified cancer cells that secrete a protein called GM-CSF. Knowledge gained from GVAX cancer vaccine trials could help to guide the clinical development of VEGFC vax.

The research team is optimistic about the potential of VEGFC vax to benefit patients. Their pre-clinical data suggested that it could be more potent than the GVAX vaccine, due to its lymphogenic action.

Another advantage of their vaccine is that it can be given in a remote location from the tumor. This characteristic is important because it could potentially target tumors that are inaccessible, or be given after a surgery to treat any possible undetected tumor cells that spread through the body. The ability of this vaccine to induce broad, tumorspecific T-cell immunity against melanoma in a mouse model makes it a strong candidate for clinical testing.

Sasso et al., Science Advances 7:1-13, 2021

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Research

Developing new approaches for acute myeloid leukemia patients Wendy Stock, MD (courtesy: Jean Lachat)

Acute myeloid leukemia (AML) is a type of blood cancer caused by genetic mutations in myeloid cells, a type of innate immune cell that helps to fight infection. Mutations in a gene called FLT3 are common in AML, and patients with these types of mutations typically have lower rates of survival. These mutations cause the FLT3 protein to be overactive, driving rapid cell proliferation and preventing death. Recently, it was shown that blocking function of the FLT3 protein kinase with a drug called midostaurin improved patient survival. This drug has now been approved as part of a treatment regimen for patients with FLT3-mutant AML. Although this drug can slow down disease progression in these patients, AML cells can become resistant to the drug as they continue to acquire additional FLT3 mutations.

Wendy Stock, MD, Anjuli Seth Nayak Professor in Leukemia, and her clinical research team hypothesized that combination therapies that attack multiple growth and survival pathways in AML may strengthen treatment strategies. The team has shown that a protein called MELK can be abnormally expressed in AML cells, and like FLT3, it is associated with poor outcomes for patients. Importantly, they found that a MELK inhibitor, a drug called OTS167, was effective at blocking MELK activity.

Accordingly, an ongoing Phase I clinical trial is testing the safety and activity of this drug in patients with relapsed or refractory AML. The team hypothesized that OTS167 may be effective against FLT3mutant AML. To test this premise, they treated human FLT3-mutant cell lines with the MELK inhibitor and found that OTS167 treatment promoted cell death, suggesting that MELK was somehow involved in FLT3 activity. Further testing revealed that treatment with the MELK inhibitor reduced the amount of FLT3 protein and reduced the activity of FLT3 and its downstream pathways in AML cells.

Combined treatment with MELK inhibitors and FLT3 kinase inhibitors blocked AML progression in a mouse model. The ability of the MELK inhibitor to effectively block numerous FLT3 kinase growth and survival pathways in AML cells suggests that it is a potential therapeutic option for FLT3-mutant AML. Eisfelder B et al., Blood Cancer Journal 11:1-15, 2021

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University of Chicago Medicine Comprehensive Cancer Center

Advancements in radiotherapy open the door to new approaches Ralph Weichselbaum, MD (courtesy: Eddie Quinones)

Radiotherapy is a common treatment received by about half of all cancer patients. Although radiotherapy is a powerful tool to control and kill cancer, malignant cells can become resistant to treatment and continue growing. Advancements in radiotherapy are needed to provide improved treatment options for patients. Research led by Ralph Weichselbaum, MD, Daniel K. Ludwig Distinguished Service Professor and Chair of Radiation and Cellular Oncology, and collaborators has revealed new strategies to improve radiotherapy-based treatments.

In a recent investigation, the researchers described a mechanism of resistance to radiotherapy caused by a type of blood cell, called Ter cells, that release a peptide known as artemin into the bloodstream, which helps cancer cells survive and spread. This collaborative study co-led

by Weichselbaum used animal models and samples from three different groups of patients who had received some combination of radiotherapy and chemotherapy, immunotherapy and radio-immunotherapy for various forms of cancer, including lung cancer and melanoma.

They found that combination treatments with both radiotherapy and immunotherapy could deplete Ter cells and reduce artemin levels in a mouse model, limiting the growth of tumors. In patients, reduced numbers of Ter cells and reduced levels of artemin were associated with improved outcomes in patients receiving radiotherapy, radioimmunotherapy and immunotherapy.

In a separate study, Weichselbaum and collaborators uncovered specific changes to the microbiome that influenced the response to radiotherapy.

Their experiments involved the manipulations of the microbiomes of mice using various antibiotics to deplete different types of gut bacteria.

One type of antibiotic tested, vancomycin, eradicates gram-positive bacteria, one of two broad classes of bacteria. This antibiotic enhanced responses to radiotherapy in mice, whereas a different antibiotic, gentamicin, which targets gram-negative bacteria, did not have that effect.

Together, these studies suggest that radiotherapy protocols may be combined with other types of treatments to improve options for patients.

Hou Y et al., Science Translational Medicine 13:1-14, 2021 21

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2021 Annual Report

Research

Diversity improves search for genetic markers of breast cancer risk Dezheng Huo, PhD

Breast cancer is the most common cancer in women worldwide and is linked to genetic risk factors. Knowing what these genetic risk factors are is critical for identifying individual patient risk. Most genome-wide association studies (GWAS) have been limited to populations with European ancestry. This may limit how information can be applied to other groups. Researchers have now compared genetic data from African- and Europeanancestry populations and identified new regions of the genome that are associated with breast cancer risk.

To address the need for genetic information about breast cancer across ancestry populations, Dezheng Huo, PhD, professor of public health sciences and medicine, and collaborators analyzed GWAS data sets of both African-ancestry and European-ancestry women. Each study compared the genomes of women with and without breast cancer to identify genetic variants or mutations that may play a role in cancer.

This study included data from African-American, Afro-Caribbean and African women.

The European cohort was large, with genetic data from more than 220,000 women. However, it was not until researchers compared it with a smaller data set of around 19,000 women of African ancestry that they identified seven regions on the genome that had previously been overlooked for cancer risk. Once the variants were identified in the African-ancestry population, researchers were also able to find them in the European-ancestry group and show that they were associated with breast cancer risk in that population as well.

Previous studies have identified genes associated with increased breast cancer risk, including BRCA1 and BRCA2. However, these two genes only account for a small proportion of cancers. This study uncovered genetic risk variants with the potential for clinical applications and demonstrated the importance of diversity in genetic research. Future studies may evaluate these variants for breast cancer risk prediction, particularly in African-ancestry populations.

Adedokun et al., Nature Communications 12:1-8, 2021

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University of Chicago Medicine Comprehensive Cancer Center

EDUCATION THAT’S RELENTLESS

2021 Annual Report

Education

Trainees of the Cancer Center’s 2021 summer research pathway programs.

Next-generation cancer researchers High school and college trainees explore exciting careers in cancer

In summer 2021, the UChicago Medicine Comprehensive Cancer Center launched two new pathway programs, expanding an already rich landscape of training opportunities for aspiring cancer researchers and clinicians. Both programs receive funding from the American Cancer Society.

SHE (Summer Healthcare Experience) in Oncology is a multi-institutional research training and career exploration program for high school women. This two-week, virtual program “provides a unique experience where young female-identifying leaders have the opportunity to be mentored by prominent women in the field and also work collaboratively and conduct research with students from other participating institutions,” said M. Eileen Dolan, PhD, professor of medicine and Deputy Director of the Cancer Center. Nearly 80 young women enrolled in the program through the cancer centers of the University of Chicago, the University of Kentucky, the University of Michigan and the University of Pennsylvania.

The Diversity in Cancer Research (DICR) program welcomed four UChicago undergraduates for an immersive summer research experience plus year-round skill-building and career development activities. In summer 2022, the program will expand to undergrads outside of UChicago and, in addition to advanced research training, offer opportunities in leadership development, community outreach and individualized mentorship for postbaccalaureate transitions.

SHE and DICR complement the Cancer Center’s well-established Chicago EYES on Cancer program for high school students, high school science teachers and undergraduates, and the researcHStart program for high school students. Collectively, the programs serve more than 50 trainees at UChicago’s campus each year, most from populations underrepresented in the sciences. The programs thrive on the expertise and generosity of the UChicago scientific community, whose members volunteer as mentors, research supervisors, workshop facilitators and guest speakers.

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University of Chicago Medicine Comprehensive Cancer Center

In 2021, the Cancer Center created a new membership category, trainee associate, for graduate and medical students, and postdoctoral and clinical fellows. Membership formally engages trainees in UChicago’s cancer research enterprise, connecting them to the robust network of faculty advancing basic, clinical, translational and population-based cancer research. Trainee associate members gain access to leadership and career development programming, award and scholarship opportunities, specialized seminars and symposia and a growing alumni network.

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2021 Annual Report

New membership category for trainees

Awards

Graduate student Juan Apiz-Saab (pictured with Kunle Odunsi, MD, PhD), received a 2020-21 Annual Diversity, Equity and Inclusion (DEI) award for outstanding accomplishments in DEI. Paula Viza Gomes (pictured with Michelle Le Beau, PhD, left, and mentor Sonia Hernandez, PhD, right) was the first-ever recipient of the Michelle Le Beau, PhD, Aspiring Scientists Fellowship. Paula received $2,500 to support her summer research at UChicago. As part of the fellowship, she also served as a peer mentor for EYES and researcHStart trainees.

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Spotlight Erica Langley

Erica Langley got back into the gym after breast cancer treatment to train for bodybuilding competitions. (courtesy: Mark Black)

Bodybuilder thrives despite breast cancer When Erica Langley walked into the gym for the first time after her breast cancer surgeries, she felt overwhelmed.

Two years earlier, the Bronzeville woman had begun pursuing her dream of being a competitive bodybuilder. A surprise breast cancer diagnosis derailed her plans, and then the COVID-19 pandemic closed her gym. When she finally resumed bodybuilding training in November 2020, she was 50 pounds heavier, weakened from chemotherapy and two surgeries.

“Mentally, I still really wanted to do this, but my body was struggling.

After the first few workouts, I didn’t think I’d ever be competition-ready,” she said. “So, I made up my mind that I was going to do this. I decided I wasn’t just going to survive cancer, I was going to thrive.”

Langley first noticed a hard lump the size of a peach pit in her breast after a workout in 2018. When it didn’t go away, she visited a neighborhood health clinic. A mammogram detected HER2-positive cancer in two locations in her left breast.

The breast cancer team at UChicago Medicine devised an aggressive and comprehensive treatment plan for Langley. Because she was only in her late 30s, she was referred for genetic testing.

The results showed a common mutation in the p53 gene, which can be inherited or acquired.

Langley’s treatment plan included 20 weeks of chemotherapy, followed by a double mastectomy, intravenous targeted therapy and, finally, reconstructive surgery on both breasts.

Langley’s return to the gym in November 2020 was the next obstacle. At first, she got tired easily and could barely do a 55-pound squat.

Within six months, she worked up to a 275pound squat. She also stuck to a strict low-carb, high-protein diet that included eating plain chicken six times a day.

In May 2021, after months of intense training, Langley entered two bodybuilding competitions and won multiple medals, placing first in one category and even surpassing competitors who had spent years competing and training.

“She showed courage and resilience, both mentally and physically,” said oncologist Olwen Hahn, MD.

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University of Chicago Medicine Comprehensive Cancer Center

A TEAM THAT’S RELENTLESS

2021 Annual Report

Cancer Center

Awards & Honors

Leaders in their fields In 2021, many of our members were recognized with some of the top awards and honors for their world-renowned expertise in cancer research.

Kunle Odunsi, MD, PhD

Jeffrey Hubbell, PhD

• Named the AbbVie Foundation Director of the UChicago Medicine Comprehensive Cancer Center

• Elected to the American Academy of Arts and Sciences

• Named the AbbVie Foundation Distinguished Service Professor in the Department of Obstetrics and Gynecology • Awarded the Society of Gynecologic Oncology 2021 Innovation Award • Named on the Illinois Science and Technology Coalition list of “2021 Researchers to Know”

Sonali Smith, MD • Named the first female Section Chief of Hematology/ Oncology in the Department of Medicine • Received the 2021 Ameri­c an Society of Clinical Oncology Excellence in Teaching Award • Named the first female chair of the Lymphoma Research Foundation Scientific Advisory Board

Maryellen Giger, PhD • Received the 2021 SPIE Directors’ Award from the International Society for Optics and Photonics

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Michelle Le Beau, PhD • Received the 2021 Gold Key Award from the Medical & Biological Sciences Alumni Asso­ciation

University of Chicago Medicine Comprehensive Cancer Center

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2021 Annual Report

Everett Vokes, MD • Elected President of the American Society of Clinical Oncology for the 2021-22 term

Olufunmilayo Olopade, MD • Elected to the National Academy of Sciences • Received the William L. McGuire Memorial Lecture Award

Tara Henderson, MD, MPH • Elected to the American Society for Clinical Investigation • Named to lead pediatric cancer and blood diseases programs at UChicago Medicine, Chicagoland Children’s Health Alliance

S. Diane Yamada, MD • Named 53rd President of Society of Gynecologic Oncology

Aytekin Oto, MD, MBA • Elected to the American Institute for Medical and Biological Engineering College of Fellows • Named Dean for Clinical Affairs at UChicago Medicine

Ernst Lengyel, MD, PhD • Received the National Cancer Institute Outstanding Investigator Award 29

Cancer Registry Report

The UChicago Cancer Registry collects, maintains and reports detailed information for pediatric and adult patients diagnosed with, and treated for, cancer at the University of Chicago Medicine and the University of Chicago Medicine Comprehensive Cancer Center at Silver Cross Hospital.

A dedicated team of data management specialists provides important data services to advance basic, translational and clinical research at our nationally recognized American College of Surgeons-approved clinical cancer program.

Registry data are essential for not only advancing research to improve patient care, but also for cancer program development, community outreach activities and decision-making in oncology and public healthcare policies.

The data presented here is from 2020. Data from 2021 will be available later in 2022.

Patient Demographics Distribution by race shows that our patient population is predominately White (2,483 patients, 62%), followed by Black (1,093 patients, 27%) and Hispanic (233 patients, 6%). These trends are similar to those seen in recent years.

Asian 3%

Unknown 2%

Hispanic 6%

Race & Ethnicity Black 27%

White 62%

Patient Geographics The majority of patients (3,264, 81%) seen in 2020 were Illinois residents. Nearly 19% (757 patients) of the total number of patients first seen in 2020 lived in other states, primarily in the neighboring states of Indiana (597, 79%), Michigan (47, 6%) and Wisconsin (22, 3%).

We also served one international patient from Ecuador.

MI 47

IL 3,264 WI 22

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University of Chicago Medicine Comprehensive Cancer Center

IN 597

Incidence by Type In 2020, 4,022 patients were diagnosed and/or treated at the University of Chicago Medicine.

This included both malignancies and benign central nervous system neoplasms. Of these, the majority of patients (3,363, 84%) were newly diagnosed, and the remaining (659, 16%) are documented in the registry for recurrent or progressive disease or the registry does not have information on the first course of treatment. The most frequently seen cancers representing 18% (734) were of the digestive system.

TYPE

MALE

FEMALE

Digestive 734 Breast 551 Male Genital System 499 Respiratory System 380 Female Genital System 300 Q@Urinary System 271 Head & Neck 217 Lymphoma 217 Endocrine* 193 Leukemia 175 Brain & CNS† 125 Myeloma 104 Skin 101 Miscellaneous‡ 66 Mesothelioma 44 Soft Tissue 31 Bones & Joints 6 Eye & Orbit 5 Kaposi Sarcoma 3 TOTAL: 4022

600

500

400

300

200

100

0

100

200

300

400

500

600

*Endocrine includes benign pituitary adenomas. † Brain & CNS includes benign central nervous system neoplasms. ‡ Miscellaneous includes blood dyscrasias, myelodysplastic/myeloproliferative syndromes and cancers with other histology/primary site designations.

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2021 Annual Report

Cancer Center

In 2021, we welcomed the following new members to our research team: Full Members

Ayman Al-Hendy, MD, PhD

Mariam Nawas, MD

Briseis Aschebrook-Kilfoy, PhD, MPH, MA

Kunle Odunsi, MD, PhD

Brandon Faubert, PhD

Ardaman Shergill, MD, MSPH

Daniel Olson, MD

Yasmin Hasan, MD Associate Members

Trainee Associate Members

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Lindsay Alpert, MD

Josephine Kim, MD

Summer Hanson, MD, PhD

Kathryn Mills, MD

Sarah Ackroyd, MD, MPH

Vishesh Kothary, MD

Raanan Alter, MD

Ruoxi Liao, BS

Nicholas Asby, BS

Jiajun Luo, PhD

David Banks, BS

Margo MacDonald, BS, MS

Santiago Bedoya, BS

Jason Meier, BS

Damian Berardi, PhD

Nabiel Mir, MBBS

Emma Brett, PhD

Rosemary Morman, PhD

Kirk Cahill, MD

Perry Morocco, MD

Kasturi Chakraborty, PhD

Anand Patel, MD

Min Chen, PhD

Sid Ramesh, BS

Mohansrinivas Chennakesavalu, BS

Caner Saygin, MD

Muhammad Ashique Haider Chowdhury, MPH, MBBS

Mohammad Shahriar, MPH, MBBS

Lindsay Schwartz, MD

Michele Ciboddo, MD

Divya Sood, MD

Chang Cui, PhD

Lizeth Tamayo, MPH

Kunal Desai, MD, MBA

Adhimanyu Thakur, PhD

Madeleine Durkee, PhD

Yu Tian, PhD

Robert Gruener, PhD

Charles Vining, MD

Katrina Hawley

Raven Watson

Emily Higgs

Adam Weiss, BS, MS

Jacobi Hines, MD

Emma Wilkinson, BS

Frederick Howard, MD

Dongbo Yang, BS, MS

Yifei Hu, BS

Jovian Yu, MD

Rosemary Huggins, BS

Anqi Yu, BS

Matthew Jotte, BS

Fangyuan Zhao, BS

Alec Kacew

Allen Zhu, BS

University of Chicago Medicine Comprehensive Cancer Center

Learn More

Credits

UChicagoMedicine.org/Cancer

Editor Jane Kollmer

Request an Appointment: 1-855-702-8222 Refer a Patient: 1-800-824-2282 Make a Gift: 773-702-6565 Administration feedback@bsd.uchicago.edu (773) 702-6180

@UCCancerCenter Follow us for news, events and the latest discoveries.

Cover Nishant Agrawal, MD Co-Director, Head and Neck Surgical Oncology Photographer Sandro Miller Pg. 3 Nita K. Lee, MD, MPH Gynecologic Oncologist Photographer Sandro Miller Pg. 7 S. Diane Yamada, MD Chief, Gynecologic Oncology Photographer Sandro Miller Pg. 11 Ernst Lengyel, MD, PhD Chair, Department of Obstetrics and Gynecology Photographer Sandro Miller Pg. 23 Jessica Donington, MD Chief, Section of Thoracic Surgery Photographer Sandro Miller Pg. 27 Stanley Liauw, MD Radiation Oncologist, Genitourinary and Gastrointestinal Cancer Photographer Jimmy Fishbein

Scientific Writer Tiha M. Long, PhD Editorial Advisors Kunle Odunsi, MD, PhD Drew Memmott Contributors Jamie Bartosch Bethany Hubbard Sarah Richards Megan Mekinda, PhD Alia Poulos, MA, MPP Matt Wood Design Pivot Design, Inc. Printing Active

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2021 Annual Report

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