C3 Spring 2021

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spring 2021

TOTALLY RADFLIX

A CU CANCER CENTER INNOVATION GIVES KIDS A WELCOME DISTRACTION DURING RADIATION TREATMENTS 10: PEDIATRIC CANCER DOCTOR MARK ERIC KOHLER, MD, PHD 11: Q&A WITH SABRINA SPENCER, PHD 12: DUSTIN DIAMOND AND SMALL CELL CARCINOMA 14: GRANT HELPS IN FIGHT AGAINST MELANOMA 18: THE EFFECTS OF AGING ON CANCER 20: ROCKET SCIENTIST DONATES TO PROSTATE CANCER RESEARCH

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N WS Researchers recognized by Golfers Against Cancer The Denver chapter of Golfers Against Cancer in February named three CU Cancer Center researchers as the beneficiaries of $50,000 grants for cancer research and clinical trials. Matthew Sikora, PhD, is conducting research to better understand underlying genetic predispositions to ovarian cancer; Jamie Studts, PhD, will use the funds to support research partnerships with rural lung cancer screening programs and explore opportunities to improve access to and delivery of high quality lung cancer screening across Colorado; and Jenna Sopfe, MD, is exploring the development of a standardized screening approach for sexual dysfunction in adolescent and young adult pediatric cancer survivors.

M AT T H E W S I K O R A , P H D

JA M I E S TU D TS , P H D

J ENNA SO PFE, MD

Plachy-Rubin Fund gr ants aid in br ain cancer research Three projects from CU Cancer Center researchers have received grants from the Denver-based Michele Plachy-Rubin Fund for Pilot Grants in Brain Cancer Research. Receiving $40,000 each to fund their work focused on brain cancer are Sujatha Venkataraman, PhD; and the teams of Philip Reigan, PhD, and Michael Graner, PhD; and Natalie Serkova, PhD, and Nicholas Foreman, MD, MBChB. Venkataraman will use her grant to research new treatments for ependymoma, a childhood brain tumor that is incurable in a high percentage of cases. Serkova and Foreman’s grant also will investigate ependymomas, in particular one form, PFA1, which is the most aggressive. Inflammation in the brain plays a critical role in these tumors, which means they don’t respond as well to therapies and tend to have a poor overall outcome. Reigan and Graner will use their Michele Plachy-Rubin Fund grant to examine the role of a protein called thymidine phosphorylase in glioblastoma, the most common brain tumor in adults.

PH IL IP R E IG A N , PH D

M I C H A EL G R A N ER , P H D

N ATA L I E S ER K O VA , P H D

S UJ ATHA VENKATARAMAN, PHD

NI CHO LAS FO REMAN, MD

Get more CU Cancer Center news on our blog: n e w s . c u a n s c h u t z . e d u / c a n c e r- c e nte r

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Looking to stop cancer in its tr acks Cancer Center research investigates origins of metastasis New research from the lab of Heide Ford, PhD, CU Cancer Center associate director of basic research, and Michael Lewis, PhD, from Baylor College of Medicine, may give doctors a better understanding of one mechanism by which cancer spreads (a process known as metastasis), and of potential ways to slow it down.

$500,000 gr ant supports pancreatic cancer multi-disciplinary care In February, the CU Cancer Center received a $500,000 grant from Canopy Cancer Collective to support the Cancer Center’s participation in the pancreatic cancer learning network aimed at improving multi-disciplinary care. The Canopy Cancer Collective brings multiple institutions together by way of a novel “learning network” to explore ways to improve multidisciplinary care. In addition to the CU Cancer Center, the collective’s inaugural cohort includes the Fred Hutchinson Cancer Research Center, Johns Hopkins Oncology Center, Mass General Cancer Center, Northwell TRACEY SCHEFTER, MD Health Cancer Institute, and Stanford Medicine Cancer Institute. Tracey Schefter, MD, professor of radiation oncology, is the physician champion, and Cheryl Meguid, NP, is the coordinator of the grant.

H E ID E F OR D , P H D

The transformation happens when cells called epithelial cells, which are more adherent to one another and less likely to spread to other parts of the body, start to take on the characteristics of mesenchymal cells, which are more migratory and more likely to invade other parts of the body. “When the epithelial cancer cells take on these characteristics of mesenchymal cells, they become less attached to their neighbor and they become more able to degrade membranes, so they can get into the bloodstream more easily,” Ford says.

CU Cancer Center brings on associate director for informatics and data science A 13-year veteran of the National Cancer Institute (NCI) has come to the University of Colorado Cancer Center to help lead efforts to develop and apply data science and artificial intelligence and methods to advance research and improve clinical practice.

The metastasis process occurs when cells that have undergone the epithelial-to-mesenchymal transition start “talking” to cells that haven’t, making those cells more likely to gain metastatic properties. Ford, Lewis, and their researchers found the crosstalk is facilitated by a naturally occurring protein called VEGF-C. If you can inhibit production of VEGF-C, you can significantly slow metastasis.

Sean Davis, MD, PhD, who most recently SEAN DAVI S, MD, PHD served as a senior associate scientist at the NCI, is the new associate director for informatics and data science at the CU Cancer Center and professor in the divisions of medical oncology and hematology in the Department of Medicine. Davis also is the inaugural Rifkin and Bennis Endowed Chair in Cancer Bioinformatics, made possible by a generous gift from the Rifkin Foundation. He joins the newly formed Center for Health AI at the University of Colorado School of Medicine.

The researchers are now in the early stages of animal trials to find out the best way to target that signaling pathway in order to better inhibit metastasis. They want to find out if they can stop metastasis from happening at all, and if they can slow its progression in patients in whom the metastatic process has already begun — and to see if they can inhibit tumor growth at the secondary site.

“Biomedical research and its clinical translation are now data-intensive efforts. Identifying connections within and between datasets is key to success in precision medicine, improving health and understanding disease,” Davis says. “The rapid advancements we have made in generating and collecting research and clinical data have led to new opportunities and challenges for researchers and patients alike.”

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Totally Radflix!

CU Cancer Center technology gives young patients distraction, comfort, and a sense of control during radiation therapy. By Greg Glasgow Thirty days of radiation treatments — five days a week, with Saturdays and Sundays off — are difficult for even the toughest of adults. But for a child, they’re even harder to bear. They often involve fasting, waking up early, having your head secured to the table, and lying in a dark room alone, without even your parents there for support. But if during treatment you can take a trip to Agrabah to hang out with Aladdin, Jasmine, and the rest of the characters in Disney’s live-action version of “Aladdin,” it makes the sessions a lot easier to handle — not to mention it makes time go by a lot faster. Thanks to a new innovation at the CU Cancer Center, patients like 5-year-old Piper Lardes are able to do just that — watch their favorite show or movie during their treatment to

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P ho t o by C a t ch I t I n TI m e

make the whole experience just a little easier. The technology, called Radflix, has a calming effect on parents as well. “It made us feel secure knowing that Piper was doing something that she enjoyed or brought her joy during a time that’s really scary,” says Doug Lardes, Piper’s dad. “We could hear the music from the movies in the control room, which made us feel like we were in there, even though we were separated by a 2-foot-wide lead door. We couldn’t see her, but we could hear her in there and share those same experiences.” Adds Piper, “It kept me company.” She is undergoing treatment for a Ewing sarcoma tumor that is pressing against her spinal cord.

The attraction of distraction Created in 2018 by Douglas Holt, MD, chief resident, and Brian Miller, PhD, medical physicist in the Department of Radiation Oncology at the CU Cancer Center, Radflix was born when Holt and Miller learned about using videos to distract young patients during other types of treatment.

P i pe r L a r de s w i t h he r parents , Doug and Bai l ey.

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“I thought, ‘This is genius. Why aren’t we doing this?’”

been fantastic. When the treatment’s over, the kids often

Holt says. “So we started looking into the process of

don’t want to get off the table. They want to stay and watch

how to do it.”

their show, which is usually not the case. Historically, they

But devising a video system for use during radiation

want to get out of there as quick as they can.”

treatments was a challenge. You can’t just put an iPad

Comfort levels

hit the device, potentially causing damage to the iPad

In the case of Ellie Songer, who was just 8 when she

and, more importantly, changing the way the radiation

started six weeks of radiation therapy for a rosette-forming

treatment dose is targeted within the patient.

glioneuronal tumor, Radflix provided not only a distraction,

After a lot of trial and error, they came up with a system

but a sense of comfort and familiarity during a process that

that used a radiotransparent projector screen that allows

can be scary and intimidating — especially for children.

radiation to pass through it. Miller designed a multi-lens

Spending time with the familiar characters on screen helped

custom long-throw projector system that shoots the

her feel less alone.

image from a long distance to keep the image relatively

“I thought it was nice,” says Ellie’s mom, Tiffany Songer. “It

small, allowing it to be mounted on the foot of the

was something that she could do to distract her while she

radiation table and travel with the patient as the table is

was in there so she didn’t just have to lie there and think too

moved. The patient chooses their favorite show or movie

much. It makes it easier on the parents, too. It’s comforting

and watches it for the duration of the treatment, picking

for us to know they’re not in there just freaking out, that

up where they left off during their next session.

they’re more comfortable watching a show that they enjoy.”

“We can set up and load the system in about a minute,”

Holt says the technology has yet another benefit —

Holt says. “It’s all wireless, it takes 20 seconds to take

helping kids who are receiving treatment to stay still during

down, and there’s an Apple TV outside the room where

treatment. It’s a task that typically is accomplished in

the radiation therapists can manipulate everything. It’s

younger kids using anesthesia.

Phot o cou rt e sy of Tif fan y So nge r

over a kid’s face, Holt explains, as the radiation would

ELLI E SO NGER

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“It’s amazing to see how with the video distraction, they just relax and quit moving,” he says. “If we can reduce the age at which you need anesthesia, that’s an end goal in and of itself. Thirty days of anesthesia is a lot for anyone to take.” Piper’s mom, Bailey Lardes, agrees wholeheartedly. It was hard enough to see Piper restrained to the table during treatment, even if it was in a special mask decorated by radiation lab techs to look like Wonder Woman. (Piper wore a matching costume to several of her treatments.) Anesthesia would have added a whole new set of complications. “That’s huge, and we were grateful for that every time,” Bailey says. “I think if we hadn’t had the Radflix, there would have been a much greater risk for having to go under.”

Improving the patient experience Though the Radflix team occasionally uses the technology on adults — those with claustrophobia or a fear of being isolated — it’s primarily targeted at patients between the ages of 3 and 18. Holt and Miller have applied for a patent and are working with the CU Innovations team to find a company interested in making Radflix a commercial product, but for now they have set up a nonprofit consortium to share the plans with other medical centers, who can then purchase their own hardware and set up a Radflix system for their young patients. So far, they have seen interest from Ohio State University, the University of Pittsburgh, the New York Proton Center, and St. Jude Children’s Research Center, among others. “Seeing the impact it has on the patient experience, it’s something that should be out there for every kid,” Holt says. “It’s that big of a deal.”

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Photo c our tes y of Ti ffany Songer

For Piper, the combination of Radflix and the radiation techs who started to feel like family made her radiation treatments, in some ways, something to look forward to. “She wanted to see the techs, she knew she was going to watch something she enjoyed, and she knew she was safe,” says Piper’s dad, Doug. “When you put those three things together, it gives a lot of empowerment for a kid. In a way, I’m almost dumbfounded that it’s not something that’s in every single location where kids and even adults are getting radiation. It’s amazing. In a time when you have no control over your body, having that much choice and control is huge. She gets to choose her movie, she gets to tell us how to walk to the radiation room — it’s choice through joy and positive things.” Holt sees the technology as part of a growing movement that finds physicians as dedicated to caring for patients as they are to curing them.

Pho to b y Ca t ch I t I n TI m e

E llie So n g e r t a lk s t o t e c h n ic ia n s be f o r e he r r a di a t i o n t r e a t m e nt .

D o ugl a s H o l t , M D , l e f t , a nd B r i a n M i l l e r, P hD , de v e l o pe d R a df li x i n 2018 after l earni ng a bo ut usi ng v i de o s t o di st r a ct y o ung pa t i e nt s dur i ng other types of treatment.

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DEC “It’s not just treating the disease; it’s about providing the best patient experience, too,” Holt says. “Even though we treat their tumors, and hopefully most of them respond, they still take with them afterward the stress of going through this whole process. PTSD levels are high in pediatric patient survivors and even higher in their parents. It’s something that is not addressed as much as it should be.”

Something to look forward to Even though Radflix has been around for more

DING CANCER

Top 5 Cancers Affecting Children — and Their Symptoms Acute Lymphoblastic Leukemia (ALL) Bone and joint pain Fatigue and weakness Bleeding and easy or unusual bruising Fever Weight loss/decreased appetite

than two years at this point, Holt is still amazed at the power something as simple as another viewing of “Moana” has on a young cancer patient. “It’s just a big boon. Even when we do consults next door at Children’s Hospital, sometimes part of our talk with the kids is, ‘Hey, when you

Brain Tumors Headaches Dizziness Balance problems Vision, hearing, or speech problems Frequent vomiting, especially first thing in the morning

get radiation, you get to watch your favorite movie.’ Often they’ll say, ‘Can we go right

Neuroblastoma

now?,’ which is just unheard of. There are

Impaired ability to walk, decreased energy

some great studies out that go through the

Pain in various locations of the body — often severe

experiences of these pediatric patients and

Diarrhea

their families, and it’s not a good experience.

High blood pressure Weight loss

“It’s not just treating the disease; it’s about providing the best patient experience.”

Wilms Tumor (Kidney Cancer) Swelling or lump in the belly — usually painless Fever Pain Nausea Poor appetite

They can dread going. It’s an adult hospital; it’s not kid-friendly; it’s nothing to look forward to; it’s gray and dreary. Now they have something to look forward to and get excited about. It’s made things a lot better for these kids.”

Lymphoma Swollen lymph nodes in neck, armpit, or groin Weight loss Fever Sweating or night sweats Weakness Flushed face Itching

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MD

CLINICAL

CARE

Double Threat

Eric Kohler, MD, PhD, combines research and clinical care in the fight against pediatric blood cancer. By Valerie Gleaton Mark Eric Kohler’s commitment to cancer research — particularly CAR T-cell therapy — and clinical care makes him a double threat when it comes to battling pediatric blood cancer.   Growing up outside of St. Louis, Kohler says he always had “a very deep fascination with biology and understanding how life works.” That interest naturally led to his decision to become a physician, but it wasn’t until his senior year of college at Rockhurst University in Kansas City, Missouri, that Kohler began to consider adding research to his career goals.   “I started doing research across town at the University of Kansas Medical Center, studying how HIV gets into the brain, and it kind of tripped this switch that I was really interested in research,” Kohler says.   Dual degrees Kohler jokes that his father “almost disowned me” when he turned down an early acceptance to medical school to spend an extra year doing research and then reapply for a dual MD-PhD program. But Kohler — a CU Cancer Center member and a researcher and physician at Children’s Hospital Colorado specializing in pediatric hematology and oncology and bone marrow transplantation — has never regretted the decision.  After graduating with a bachelor’s degree in biology and chemistry from Rockhurst, Kohler spent the next nine years earning a dual MD and PhD in tumor immunology from Medical College of Wisconsin. From there, he moved to Maryland, where he did his pediatric residency at Johns Hopkins University and a joint fellowship in pediatric hematology and oncology at Johns Hopkins and the National Cancer Institute (NCI) at the National Institutes of Health.

A happy coincidence Kohler says he knew early on he wanted to work in pediatrics and that it was a “happy coincidence” that his graduate lab work at Wisconsin focused on vaccine research for pediatric neuroblastoma.   It was during his fellowship at the NCI that Kohler dove into what would become his professional passion: a new type of immunotherapy called CAR T-cell therapy. In fact, Kohler and his colleagues ran some of the first CAR T clinical trials ever, and he says their findings were “transformative.”   “It was the realization of what we’d been trying to do throughout my entire graduate school career with vaccines, but with a very different approach and a very, very effective one,” Kohler says.   This interest in immunotherapy also influenced Kohler’s decision to specialize in hematology and bone marrow transplantation. “I found that that was where I could really apply immunotherapy the most efficiently,” Kohler explains.   Kohler and his mentor, Terry Fry, MD, were recruited to build a cellular therapy program within the Center for Cancer and Blood Disorders at Children’s Hospital Colorado in 2018. Since arriving, Kohler has been involved in the creation of a new CAR T-cell therapy that was designed, developed, and manufactured on campus. The treatment is now in clinical trials with adult patients and will soon be live in pediatric patients as well.

or high-risk leukemia who need a bone marrow transplant or CAR T-cell therapy because they are unlikely to respond to conventional chemotherapy.   “It’s got very high highs and very low lows, but it’s extremely rewarding,” Kohler says of his clinical work.  Kohler, who just got his own lab a few months ago, is excited to continue his research on CAR T cells. His latest research focuses on redesigning CAR T cells to better respond to leukemia and lymphoma, as well as applying the treatment to types of leukemia for which CAR T-cell therapy isn’t currently used, such as AML. He’s even working on a collaboration with a colleague who does brain tumor research.   “We’ve got some really exciting preclinical data about a CAR T cell that we developed against a pediatric brain tumor called DIPG [diffuse intrinsic pontine glioma],” Kohler says. “Currently it’s considered completely incurable, but we’ve got some really promising results that I think that could go somewhere in the next five to 10 years.”

Risks and rewards The physician also provides clinical care for patients at Children’s Hospital, primarily those with relapsed M A R K ERI C KO HLER, MD, PHD

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A CONVERSATION WITH SABRINA SPENCER, PHD

BY VALERIE GLEATON

CU Cancer Center Member Assistant Professor, University of Colorado Boulder Department of Biochemistry

working. But in a way, that’s a little too late. Because the question is, how did those cells survive in the first place to be able to acquire the mutations to become drug resistant? We wanted to look at the first few days of drug treatment to understand whether you can already see cells adapting in a non-genetic way in order to evade the drugs.

S A B R IN A SPE N C E R , PH D

Sabrina Spencer, PhD, is a CU Boulder researcher and a CU Cancer Center member. Spencer recently won two awards: the Damon RunyonRachleff Innovation Award (from the Damon Runyon Cancer Research Foundation) and the Emerging Leader Award (from The Mark Foundation for Cancer Research). We spoke to her about the awards and how she plans to use them to further her research. What is the focus of your research? The work is about understanding where drug resistance comes from in cancer. It’s a well-known problem, and it’s particularly prominent with targeted therapeutics. These drugs usually work great at first, but then, after some time, there’s relapse. A lot of people have focused on trying to understand what mutations in those relapsed tumors make the drugs stop

You’re watching cells become drug resistant in real time? How does that work? We use time-lapse microscopy to study this process. We’re particularly adept at time-lapse imaging of single cells, where we film single cancer cells over several days and watch them proliferating. Then we hit them with the drugs and watch the drugs block the cells from proliferating. Then, after a couple of days, we can see a subset of cells start proliferating again. What sparked your interest in this research? I’ve always been interested in outliers. And I’ve always been interested in cancer cells, because they have such an interesting mixture of adaptive and maladaptive features — features that make them proliferate faster but are an Achilles’ heel as well. I like the philosophical juxtaposition of combining that with this idea of outliers and heterogeneity. Every cell is unique. Even genetically identical cells aren’t truly identical, because they could have a little more of protein X and a little less of protein Y at any given moment. When it comes to drug resistance, these chance events can make a cell an outlier on

one particular day, and that could be the day the drug comes along. Now that cell has a completely different fate. You just won two awards to further this research. What was that like? I submitted a very similar grant application to both, because each funding agency only gives out a handful of these awards. I didn’t think this would be a problem, because I wasn’t expecting to get either one! Then I found out that I had received both and thought I’d have to choose between them, but when I reported my situation to the two foundations, they said, “Don’t you worry about it. We’ll sort it out.” And they decided to co-fund the grant. How will you use the grant? One of the things we saw about the cells that escaped the drugs — cells we have dubbed escapees — is that they have DNA damage. That’s curious, because these drugs are not supposed to be mutagenic. So the first aim of the grant is to understand how these drugs are causing DNA damage. The second finding is the activation of a stress response pathway called ATF4. That pathway is super-high in the escapees, but not the non-escapees and not the untreated cells. We know that if you knock that pathway down, you get fewer escapees, but we don’t really understand what that pathway is doing for the escapees. Is it helping them escape the drugs? Or is it just helping them survive the stress of cycling in the presence of the drugs? So that’s the second aim of the grant, to understand how this ATF4 stress response pathway is enabling or promoting drug escape.

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The actor died at age 44 from small cell carcinoma. By Greg Glasgow Actor Dustin Diamond, best known for playing the nerdy character Screech on teen sitcom “Saved By the Bell,” died February 1 at age 44. Diamond died just weeks after being diagnosed with stage 4 small cell carcinoma, a type of cancer that commonly occurs in the lungs but can also originate in the prostate or gastrointestinal tract. “In that time, it managed to spread rapidly throughout his system; the only mercy it exhibited was its sharp and swift execution,” read a statement from the actor’s management team after his death. “Dustin did not suffer. He did not have to lie submerged in pain. For that, we are grateful.

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Ro b Di Cat e ri no /W i ki med ia C o m m o ns

Dustin Diamond’s Death Proves There is Still Much For Researchers to Learn About Cancer


University of Colorado Cancer Center member Erin Schenk, MD, PhD, says small cell carcinoma — a rare cancer that often spreads aggressively E R IN SC H EN K , M D , P H D and has no associated screening procedure — is a reminder of how much work medical professionals have left to do in the fight against cancer. “Even when everyone does exactly what they should — meaning the patients bring their concerns to the attention of their doctors and their doctors do all the appropriate tests and get the appropriate therapy started — unfortunately, even in 2021, people can sometimes have an untimely death because of cancer,” says Schenk, an assistant professor in the University of Colorado School of Medicine Division of Medical Oncology. Diamond was hospitalized on January 12 after experiencing severe pain throughout his body — a sign that the cancer had metastasized, or spread, from its point of origin, Schenk says. “Often cancers don’t cause pain until they’re invading other key organs,” she says.

COVID-19 causing deadly delays

It’s unclear if Diamond was experiencing pain prior to midJanuary, but Schenk says it’s possible he had less severe, more localized pain that could have been investigated sooner. It’s not uncommon during the COVID-19 pandemic, she says, for people to put off treatment and screenings out of fear of being infected during a doctor visit. “We’re starting to learn how the COVID pandemic has really impacted not only our current cancer patients, but also the cancer patients who are getting diagnosed,” she says, “In a number of studies across the world, what’s being reported is that patients are presenting to our offices with more

advanced disease than they were pre-COVID. People putting off their usual health screenings is really going to have an impact in years to come in terms of patients being diagnosed with cancer that is more advanced, as well as other chronic, controllable diseases like high blood pressure, diabetes, and heart disease. This will set the health of the world back quite a bit.” Schenk urges anyone with unexplained, persistent symptoms such as pain to see a doctor as soon as they can and stresses that telehealth visits and local bloodtesting and imaging facilities can help ease fears about going to a hospital or clinic to seek treatment. “There’s a lot more flexibility now,” she says. “You don’t have to go to your academic medical center and get everything done there.”

Family history

Though there is no screening for the small cell carcinoma that killed Diamond, Schenk says certain subtypes of this cancer can run in families, so it’s important to have discussions with family members who were diagnosed with cancer about the type of cancer they had and at what age they were diagnosed. “Especially if they were under 50 years old, that’s often a clue to us that we might need to do some additional evaluation to really take a deep dive into the genetics of the patient and the family to see if they have predispositions to some of these cancers,” Schenk says. In the end, Schenk says, Diamond’s death was due to a rare set of circumstances surrounding a rare type of cancer, and there is still much for doctors to learn about cases like his. “This one is really hard. This one is unfortunately just a rare thing that sometimes happens in young people, where he did just not survive very long,” she says. “This is an extreme of an extreme, but it still is devastating to the family and friends and loved ones.”

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PREVENT CANCER FOUNDATION GRANT WILL HELP RESEARCHER IN FIGHT AGAINST MELANOMA Neil Box, PhD, followed a group of kids for more than 10 years to track the results of long-term sun exposure. By Greg Glasgow CU Cancer Center member Neil Box, PhD, is on a quest to decrease the deadly effects of melanoma. His Sun Bus is a fixture at many of Colorado’s biggest summer festivals, offering free skin cancer screenings and education, sun-safety products such as hats, shirts, and sunscreen, and cutting-edge technology that measures hidden sun damage. And thanks to a new grant from the Prevent Cancer Foundation, Box — an associate professor of dermatology in the University of Colorado School of Medicine — will conduct new research on the causes and predictors of the deadly skin cancer. “We know that sun exposure creates risks of melanoma, but it’s really hard to get at someone’s history of sun exposure because melanoma patients have recall bias,” Box says. “They over-remember the number of sunburns or excessive sun exposures they’ve had in the past because they get the shock of a melanoma diagnosis and they unintentionally misreport. Melanoma is such a big deal that it makes patients say, ‘I must have had heaps of sun exposure when I was a kid, because I got melanoma.’”

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“We can start to understand the relationship between number of sunburns and sun damage as it appears on the skin, and by understanding that we’ll be another step closer to actually using sun damage measures in melanoma studies directly.” ACROSS THE AGES

To get more accurate data, Box worked with Lori Crane, PhD, MPH, in the CU School of Public Health to conduct a longstanding, longitudinal study of mole development in kids. The researchers followed a group of 1,150 young people over more than 10 years to see how sun exposure contributed to mole development, and therefore, risk of melanoma. “Moles may be a biomarker for risk in later life,” Box says. “If you have a lot of moles, you have a much higher risk of melanoma. High childhood sun exposures induce the highest levels of moles in children.”

L O R I C R A N E, P H D , M P H

With the grant from the Prevent Cancer Foundation, Box, Crane, and their collaborators will do further follow-up work with the study participants to determine the results of their early sun exposure. Using a specialized camera that shines polarized wavelengths of light on the face to reveal hidden sun damage, as well as a process called skin surface microtopography, in which researchers take a silicone cast of the back of the hand to investigate the presence of lines and pores, they hope to develop even more sophisticated measures of sun damage. “It will be important in looking at some new measures of sun damage on the skin,” Box says. “We can start

to understand the relationship between number of sunburns and sun damage as it appears on the skin, and by understanding that we’ll be another step closer to actually using sun damage measures in melanoma studies directly.”

MORE ACCURATE PREVENTION

Currently, Box says, melanoma prevention and screening is based on generic sun safety recommendations, with additional cautions for those with fair or red hair color, fair skin color or freckling; those who report a history of excessive sun exposure; and patients with a history of melanoma. In his new study, he plans to explore how certain genetic markers and quantifiable sun damage measures can also be used as tools to evaluate risk of the disease. “You would think, based on genetics, that some people might need less exposure to hit some kind of melanoma threshold,” he says. “Someone who gets NEI L melanoma in their 30s probably has some elevated genetic predisposition. But somebody who gets melanoma in their 50s or 60s — which are the decades when most melanomas appear — that could be due to sun exposures that happened 40 or 50 years ago.”

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BO X, PHD

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Helping Hands Colorado Cancer Screening Program at the CU Cancer Center helps low-income patients navigate the screening process. By Greg Glasgow Pablo Garcia started to worry when he began experiencing unusual stomach symptoms. He worried even more when his doctor at the Salud Family Health Center in Longmont, Colorado, ordered a colonoscopy to check for signs of colon cancer. Pablo was unfamiliar with the procedure, the preparation, and the hospital where the test was to take place. That’s when the patient navigator team at Salud stepped in to help, educating Pablo about what a colonoscopy entails and why the test is important, scheduling him for the procedure and a follow-up appointment, and walking him through the prep. “They would call me and say, ‘Go here, go there, do this and that’ — everybody involved was very helpful,” Pablo says. “Through the whole process I never felt uncomfortable. I felt welcome.” Pablo is thankful he went in for the colonoscopy in August 2019, since the test showed he had colon cancer. He had surgery in February 2020, followed by six weeks of radiation treatment. A follow-up colonoscopy in summer 2020 showed that he was cancer-free. “All the doctors that treated me were all very professional and I appreciate that they got rid of it,” says Pablo, 66. “I’m still praying it doesn’t come back.”

Overcoming barriers to care Salud’s patient navigator team was there to help Pablo every step of the way. Supported and funded in part by the Colorado Cancer Screening Program (CCSP) at the CU Cancer Center, the team exists to help patients — most of them low-income and many of them Spanish-speaking-preferred — through the process of getting colonoscopies or endoscopies, as well as any follow-up care they may need. PA B L O G A R C I A

For more information on the Colorado Cancer Screening Program, visit medschool.cuanschutz.edu/ colorado-cancer-center/ccsp

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“It’s extremely helpful because we have patients with many barriers to care,” says Hans Elzinga, MD, a family medicine doctor at Salud who oversees colonoscopies and endoscopies. “Over two-thirds of our patients are Spanish-speaking-preferred, so the language barrier is one of the most common. All of our folks who work as patient navigators are fluent in Spanish or bilingual.”


Navigators also help facilitate transportation for patients, and they help with patient education. They even show up at the hospital on test days so patients can see a familiar face. “We have a lot of patients with lower health literacy, so the navigators provide one-on-one teaching to help them understand not only why we do the tests but also, most importantly, they help with how to prepare for the test,” Elzinga says.

The importance of early detection In addition to patients like Pablo, who come in due to symptoms, the CCSP — which is funded by the Cancer Cardiovascular and Pulmonary Disease Grants Program — works to get all patients screened as close to the recommended age as possible. The program trains and provides funding of patient navigation at “safety-net” clinics around the state — federally qualified health centers, hospitals, rural health centers, faith-based community clinics, and more — to talk to patients about the importance of getting screened for colorectal cancer, lung cancer, breast cancer, and cervical cancer based on recommended screening guidelines. “Within the medically underserved community, we still have so many people that aren’t accessing preventive or primary care in general, so that’s one of our big aims,” says CCSP director Andrea (Andi) Dwyer. “The screening rates in some communities are on the rise, but we also know communities of color, particularly F r o m le f t , p a t ie n t n a vig a t o r Ta n ia M a l do na do , M A ; H a ns El z i nga , M D ; P a bl o Garc ia ; s p e c ia l p r o c e d u r e s p r o g r a m m a na ge r L upe S a ndo v a l , R N ; a nd pa t i e nt na vig a t o r Su e Su p in s k i, M A , a t t h e Sa l ud F a m i l y H e a l t h C e nt e r i n L o ngm o nt .

African Americans, are at higher risk and have lower screening rates. We also know in our rural communities that screening rates remain low, although in some parts of the state, those populations have some of the highest rates of incidence of late-stage disease.” Dwyer also notes the COVID-19 pandemic has impacted screenings across the board. The CCSP, she says, is being more deliberate than ever about reaching the medically underserved as a statewide ban on elective screenings in spring 2020 ban created backlog and urgency. Key to the whole process, Elzinga says, are the navigators who help patients through the maze of tests, appointments, and billing procedures, demystifying the process so people get the screening they need. “Early detection has a huge advantage in colorectal cancer,” he says. “Where patient navigation has a huge benefit is when you have folks who for whatever reason have some different barriers to care. Helping with those and getting procedures done in a timely fashion is a really big deal. Time is of the essence when it comes to early detection, so getting things done sooner makes a huge difference. We’re talking lifeand-death changes in people’s lives.”

Comforting presence One of those navigators, Lupe Sandoval, who oversees patient navigation at the Salud clinic in Longmont, says it’s that ability to change and improve lives that makes the job so rewarding. “We are there to assist our patients. It’s very scary when you go somewhere and you don’t know anybody at the hospital,” she says. “They see the navigators there, they know us from consults, from various phone calls we have made to them to confirm appointments, to ask them about their meds, and I think that’s a very big comfort to them.”

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THE IMPACTS OF AGING ON CANCER A working group at CU Cancer Center is working to understand why risk of the disease increases as people get older and to address aging-associated challenges for patients. By Greg Glasgow For more than a year, a working group at the University of Colorado Cancer Center has been studying the many ways the aging process impacts cancer — including incidence, progression, and prognosis of the disease, therapeutic options and outcomes, and the psychosocial aspects of living with cancer. “Ninety percent of all cancers happen after age 50, and it increases exponentially after that,” says working group leader and CU Cancer Center deputy director James DeGregori, PhD, editor-in-chief of a new journal on cancer and aging. “Most people get cancer when they’re old, and the older you are, typically the worse your outcomes are.” That’s in part because many conventional therapies aren’t recommended for patients over a certain age, DeGregori explains, but it’s also because of social factors. Many older adults don’t drive, for example, and have a harder time getting to a clinic for treatment. The situation is even worse in Colorado, where elderly people are more likely to live in rural communities than younger people, further reducing access to care. The Aging and Cancer working group includes researchers from the Anschutz Medical Campus, University of Colorado Boulder, and Colorado State University who meet regularly to share research, exchange information, propose crossdisciplinary collaborations, and even to fund projects aimed at learning more about the influence aging has on getting, fighting and beating the disease.

J AMES De GREGO RI , PHD

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Understanding the evolution of cancer

A healthy tissue environment

For DeGregori, it’s a research interest that has lasted for more than a decade. He is particularly interested in why older bodies favor the development of cancer.

DeGregori and his team are now looking at ways to treat cancer by maintaining and restoring the body’s tissue environment.

“We are asking, ‘Why is it that someone who is more frail is more likely to get cancer?’” he says. “What is it about their body? Is it that their immune system is failing? Is it that the landscape of their tissues is more conducive to the evolution of cancer? If we understand what factors associated with getting older increase the chance of getting cancer, maybe we could develop interventions to counteract this aging-associated risk.”

“We’re learning that one of the ways you do that with therapy is by not screwing up the environments in the first place,” he says. “A lot of the more conventional therapies are incredibly toxic. They’re just devastating to a tissue environment. Sure, they kill the cancer cells, but they leave a devastating landscape. And that allows for the cancer to come back.”

Conventional cancer wisdom says the reason we get more cancer as we age is because we get more mutations, but DeGregori’s latest research shows there’s more to it than that. “It’s not just that we get more mutations, it’s also that the tissue environments change,” he says. “What my lab has shown is that a young tissue environment disfavors the evolution of cancer, and an old tissue environment favors the evolution of cancer.” He says it’s not unlike the evolution of life on Earth, which has been driven more by environmental change than by mutations. To prevent cancer, it’s important to better maintain the environment in the body by not smoking, eating well, and exercising.

His research is looking into the success of less-toxic therapies that cause deeper and longer remissions by preserving much of the tissue environment. His team also is developing interventions to prevent aging-associated cancer development, many of them anti-inflammatory treatments that partially restore the youthfulness of tissue. “Inflammation is known to go up as we get older, and we’ve shown that when we dampen that inflammation, we can also dampen the cancer evolution that would normally happen in some of our tissues,” he says. “You might think we should all be taking anti-inflammatories, but antiinflammatories have side effects. They can increase the risk of infection. If we can figure out how to do this in a more subtle way — not completely dampen down inflammation, but just bring it down to youthful levels — then we will have achieved our goal.”

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Looking for a Cure for Prostate Cancer Patient and donor Ashton Villars is passionate about funding for immunotherapy research. By Valerie Gleaton Ashton Villars has always been a problem solver. As a competitive athlete in basketball, waterskiing, and tennis, as well as an actual rocket scientist, Villars has tackled every challenge in life head on — including his prostate cancer diagnosis. Now, he’s bringing that same problemsolving spirit to supporting cancer research.

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S U P P O R T E R

F CUS

A born engineer Even as a child, the New Orleans native knew he was going to be an engineer. After earning a bachelor’s degree in mechanical engineering and a master’s in nuclear engineering from Louisiana State University, Villars worked for Boeing on the Apollo project and was on-site at NASA’s Michoud Assembly Facility on the day of the first moon landing in 1969. After that, he went back to LSU to finish his master’s thesis, then moved to Denver in the early 1970s to look for work. He eventually took a job in the research department at aerospace company Martin Marietta. “It was hard leaving New Orleans, especially because of the food,” Villars jokes. “I try and go back once a year to partake of that. Even though it’s not healthy, it sure tastes good!”

Doing his own research In late 2007, Villars’ prostate-specific antigen (PSA) levels began to escalate. Elevated PSA levels can signal a number of prostate issues, including cancer. A biopsy in January 2008 confirmed that Villars had prostate cancer and that it was likely metastatic.

ASHTO N VI LLARS

Although Villars was initially in a state of shock, his training as a scientist quickly kicked in. His urologist recommended he get surgery immediately, but Villars, who didn’t know much about prostate cancer, wanted time to do his own research. “Like everybody who is faced with terminal cancer, I didn’t sleep that first night,” Villars says. “But before the morning came, that all changed, and I became the engineer again.” Instead of surgery, Villars sought out a second opinion from Brian Kavanagh, MD, a radiation oncologist at the CU Cancer Center and chair of the division of radiation oncology. Together, they decided Villars would go on hormone therapy to slow the cancer and give him time to decide how he wanted to approach his treatment.

ASHTO N VI LLARS WATERSKI I NG

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Since then, Villars has visited clinics across the country, where he has undergone countless imaging scans and blood tests and numerous treatments, including both internal and external radiation, different types of hormone therapy, and surgery to address a tumor that had developed near one of his kidneys.

“Ashton’s case is an example of how the doctor and patient really are a team, as he is always bringing new thoughts, perspectives, and questions about prostate cancer to really keep me on my toes,” Kessler says. “This is one of the best parts of our work — when we can work together with patients and stay on the cutting edge.”

A clinical trial brought Villars back to the CU Cancer Center in 2017 and introduced him to his current doctor, Elizabeth Kessler, MD. Kessler is a medical oncologist and CU Cancer Center member specializing in genitourinary cancers (prostate, bladder, testicular, and kidney cancers).

Giving back

“I adore Dr. Kessler,” Villars says. “like many of the doctors at University of Colorado Hospital, she’s amazing, selfless, and tireless. And she’s put up with me quizzing her every time we talk about the next step. Because at this point, I don’t do anything without researching it.”

E L IZ A B E T H K ES S L ER , M D

The feeling is mutual, Kessler says.

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It was a tour of Kessler’s research lab in early 2019 — along with a presentation about CAR T-cell therapy by Terry Fry, MD, the CU School of Medicine’s director of cancer immunotherapy and CU Cancer Center member — that inspired Villars to begin donating to the university. “I donate because I want to help other patients as much as I possibly can. And if my donations help, it’s a win-win for me, because I’m searching for a treatment that will extend my lifespan and my quality of life,” he says. “So I’m also doing it for myself.”

TERRY FRY, MD

In addition to annual gifts, Villars will leave a legacy by giving a gift of real estate and has designated CU


Lessons Learned

as a beneficiary of his retirement account to support prostate cancer research and CAR T-cell immunotherapy research within the CU Cancer Center. He also has given gifts to support the CU Anschutz Fund for Excellence, which provides flexible funding to address CU Anschutz’s most promising priorities in support of research, education, and patient care. “I feel like giving to the University of Colorado Cancer Center is such a useful thing to do, because I know it will go to doing something to really help cancer patients and the research world,” Villars says. “Plus, I’ve always had a soft spot for UCHealth and the University of Colorado,” he adds. “Except for the times they played LSU in football!” Villars hopes his donations will help researchers achieve a breakthrough in immunotherapy for prostate cancer patients. In the meantime, he is still fighting his own battle against cancer, and, of course, doing his own research every step of the way. “Engineers, scientists, and doctors — we’re all problem solvers, and I think that’s really helped me in fighting cancer,” Villars says.

In addition to giving back financially, Villars hopes the lessons he has learned during his 13 years living with prostate cancer can help others as well. Healthy Lifestyle Don’t overlook the importance of a healthy lifestyle. Diet and exercise can have a significant impact on longevity and quality of life. Decisions The first treatment is the most important treatment! You may never recover from a bad decision. Advocating Be your own advocate and/or bring an advocate with you. Technology Scans are vital. Seek out the latest imaging technology to find and locate prostate cancer early. Testing Early Don’t underestimate the value of PSA testing early and often and tracking your levels. It can save lives.

Get more CU Cancer Center news on our blog: news.cuanschutz.edu/cancer-center

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C3: Collaborating to Conquer Cancer Published twice a year by University of Colorado Cancer Center for friends, members and the community. (No research money has been used for this publication.) Contact the communications team: Jessica Cordova | Jessica.2.Cordova@cuanschutz.edu Design: Candice Peters | Design & Printing Services University of Colorado The CU Cancer Center partners with: UNIVERSITIES

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UCHealth University of Colorado Hospital UCHealth Cherry Creek UCHealth Highlands Ranch Children’s Hospital Colorado Denver Veterans Affairs Medical Center Visit us on the web: medschool.cuanschutz.edu/colorado-cancer-center To support the fight against cancer with a philanthropic gift visit giving.cu.edu/cancercenter. The CU Cancer Center is dedicated to equal opportunity and access in all aspects of employment and patient care.

The Personal Connection T H E

M E S S A G E

My family history with cancer is my inspiration for fighting the disease. For me, the fight against cancer is personal. My father

personal commitment to fighting cancer. The CU

passed away from metastatic colorectal cancer when

Cancer Center offered this version of the phrase,

I was young, and my mom survived many decades

based upon our mission statement: “We are the CU

after being treated for breast cancer. Almost one in

Cancer Center and We Will Prevent and Conquer

two Americans will get diagnosed with a major cancer,

Cancer. Together.”

and one in four Americans will die from cancer. It’s touched all of our lives.

FROM THE DIRECTOR RICHARD SCHULICK, MD, MBA DIRECTOR, UNIVERSITY OF COLORADO CANCER CENTER CHAIR OF SURGERY, UNIVERSITY OF COLORADO SCHOOL OF MEDICINE

Please join us at Collaborating to Conquer Cancer: A Virtual Conversation Benefiting the CU Cancer Center at 5:30 p.m. on June 15. For more information, please contact lindsay.k.andrews@cuanschutz.edu or call 303-724-7823.

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We are working to put an end to 1.9 million Americans being diagnosed with cancer every year

On February 4, we joined patients, survivors,

and 600,000 dying every year. In Colorado, cancer

and health care professionals around the world

is the number-one cause of death, outpacing heart

to recognize World Cancer Day — a day to raise

disease and stroke. One of the worst things about

awareness, improve education, and catalyze personal,

cancer is how random it can be. You can live the

collective, and government action around the deadly

healthiest lifestyle, you can do everything right, and

disease. It was the perfect time to remind patients,

you can still get cancer.

health care professionals, and the citizens of Colorado of the Cancer Center’s mission and priorities.

I’m studying cancer and treating cancer patients with a selfish interest. I want to do this not only for

The World Cancer Day theme, ‘I Am and I Will,’ asked

all of us, but I want to do it for me and my family.

participants to reframe the phrase to emphasize their

We’re all in this fight together.


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