C3 Magazine Spring 2022 by University of Colorado Cancer Center

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ANIMAL INSTINCTS HOW CANCER RESEARCH IN DOGS IS IMPROVING CARE AND TREATMENT IN HUMANS 10: BREAST CANCER AND spring 2022

QUALITY OF LIFE 12: FIGHTING GLOBAL CHILDHOOD CANCER 14: BIOMARKER LEADS TO LIFESAVING TREATMENT 18: Q&A WITH WELLS MESSERSMITH 20: ENDOWMENT MEMORIALIZES MULTIPLE MYELOMA PATIENT

N WS New Leadership for CU Cancer Center Progr ams In December 2021, the University of Colorado Cancer Center announced several leadership transitions that will support the center in its mission to overcome cancer through innovation, discovery, prevention, early detection, multidisciplinary care, and education. Patricia Ernst, PhD, a professor of pediatrics and pharmacology, joins Tin Tin Su, PhD, as co-leader of the Molecular and Cellular Oncology Program, which supports researchers whose work provides insights into gene expression regulation and its deregulation in cancer, the cellular

response to genomic insults, the molecular structure of cancer-relevant proteins, and new signaling processes driving tumor growth. Stacy Fischer, MD, an associate professor of internal medicine, joins Jamie Studts, PhD, and Rajesh Agarwal, PhD, to co-lead the Cancer Prevention and Control (CPC) Program. The CPC’s work applies the expertise of behavioral, basic, and clinician-scientists to conduct innovative and impactful cancer research that reduces Colorado’s cancer burden.

PATRI CI A ERNST, PHD

STACY FI SCHER, MD

Researchers Recognized by Golfers Against Cancer

D AN SHERBENOU, MD, P H D

Three research teams at the University of Colorado Cancer Center have received $50,000 grants from the Denver Chapter of Golfers Against Cancer to support their research in fighting the disease. Golfers Against Cancer is a national organization founded in 1997 by a group of Houston golfers who started raising money for cancer research after losing two of their golfing buddies to the disease. The Denver chapter was established in 2009, with donations from events going to fund research at the CU Cancer Center. We are grateful to Golfers Against Cancer for their strong partnership with the CU Cancer Center and their ongoing support of cancer research.

S U J ATHA VENKATARAMAN, PHD

The CU Cancer Center awardees are: • PETER FO RSBERG, M D

The research team of Dan Sherbenou, MD, PhD, and Peter Forsberg, MD, will use the funds to evaluate a laboratory test for its potential to help pick the best treatments for patients who have relapsed multiple myeloma.

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Jordan Jacobelli, PhD, seeks to inhibit leukemia infiltration and colonization of the central nervous system to prevent relapses in patients with acute lymphoblastic leukemia (ALL).

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The team of Sujatha Venkataraman, PhD, M. Eric Kohler, MD, PhD, and Masanori Hayashi, MD, will apply their funding to the further development of gene-edited CAR-T cells as a novel treatment for metastatic Ewing sarcoma, a rare cancer that occurs most often in children and young adults.

JORDAN JACOBELLI , PH D

M . ERI C KO HLER, MD, PHD

MASANO RI HAYASHI , 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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New Leadership For Clinical Trials

Cancer Clinical Trials Office Welcomes New Medical Director The University of Colorado Cancer Center in February welcomed Marie Wood, MD, as medical director of the Cancer Clinical Trials Office (CCTO). In her new role with M A R IE WOO D , M D CCTO, Wood says she looks forward to meeting and collaborating with colleagues “to see if we can increase accrual to trials that we have and make sure we have the right trials open,” she says. “Another goal is to see if we can increase diversity among our accruals, which can be a challenging thing to do. “I know the CU Cancer Center has been really focused on this and made some great inroads, so we’re going to work to ensure those are sustainable. Considering things like distance, cost, and time are going to be important as we’re trying to increase accrual among underrepresented groups, especially those living in rural areas.” Returning to Colorado is a homecoming for Wood, who completed her medical school and fellowship training at the University of Colorado School of Medicine and stayed on as faculty for five years. She then joined the University of Vermont and University of Vermont Cancer Center before returning to Colorado. She brings more than 30 years of clinical and research expertise to her role. Wood also serves as clinical director for breast medical oncology. She sees patients at CU Anschutz Medical Campus and Highlands Ranch Hospital.

RENEWAL NEWS

The National Cancer Institute renewed the CU Cancer Center’s “comprehensive” designation in March. Read more about the renewal and what it means in the note from CU Cancer Center director Richard Schulick, MD, MBA, on the back cover.

Immunother apy Research Receives Significant Support From R01 Gr ant University of Colorado Cancer Center member Yuwen Zhu, PhD, associate professor of surgery at the CU School of Medicine, is researching ways to normalize tumor vasculature — the tumor’s network of blood vessels — improving pathways to the tumor so drugs and the body’s immune killer cells can better reach and attack the disease. His groundbreaking immunotherapy research focused on tumor vascular normalization recently gained significant support from a National Institutes of Health Research Project Grant (R01). The research has the potential to treat a wide array of cancers. The R01 grant will support the research Zhu has been conducting for more than 12 years. He and Richard Schulick, MD, MBA, director of the CU Cancer Center, along with Zhu’s former colleagues at Yale University, have a pending patent application for methods of treating a tumor by administering an agent to block a particular signaling pathway.

YUW EN ZHU, PHD

Wings of Hope Funds Pancreatic Cancer Research Two research investigations led by University of Colorado Cancer Center researchers received grant support from Wings of Hope for Pancreatic Research. CARLO MARCHETTI , PHD

Carlo Marchetti, PhD, an assistant research professor of infectious disease, and Todd Pitts, PhD, an assistant research professor of medical oncology, received $50,000 for pilot grant funding to support their research on the role the NLRP3 protein plays in pancreatic ductal adenocarcinoma progression, and Sana Karam, MD, PhD, an associate professor of radiation oncology, received $300,000 in pilot grant funding for research studying the use of targeted radiation therapy in combination with a therapeutic that inhibits the STAT3 protein from promoting tumor cell survival in pancreatic cancer. We appreciate Wings of Hope and the community of supporters they have built over the past decade in the fight against pancreatic cancer. They have been steadfast supporters of and advocates for the CU Cancer Center.

TO DD PI TTS, PHD

SANA KARAM, MD, PHD

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Beyond Frisbee and Fetch Collaborations between CU Cancer Center and CSU Flint Animal Cancer Center researchers lead to cancer therapies with the potential to benefit humans and companion animals.

By Rachel Sauer

Molly was a fan of cookies. Whenever there was a plate of them nearby, she kept her eye on it, waiting for her chance to sneak one or five. She was a fan of water, too, even after she had surgery to remove her left front leg following an osteosarcoma, or bone cancer, diagnosis in April 2017. In the 16 months that Molly lived after her surgery, the Denver golden retriever enjoyed treats, watching squirrels, and basically everyone she met. Molly’s person, Savannah Halboth of Denver, credits not just Molly’s good nature and happy outlook for those unexpected 16 months, but her participation in a clinical trial at the Flint Animal Cancer Center (FACC) at Colorado State University (CSU), led by University of Colorado Cancer Center members Steven Dow, DVM, PhD, and Dan Regan, DVM, PhD, both faculty members at CSU. The success of that trial treating bone cancer in dogs led to collaboration with other researchers at the CU Cancer Center, as well as Children’s Hospital Colorado. Using data from the canine trial, researchers including Lia Gore, MD, co-leader of the CU Cancer Center Developmental Therapeutics Program, designed a similar trial treating pediatric bone cancer patients. This trial is one of many examples of not just the collaboration and partnership between CU Cancer Center members around the state, but the overlaps between humans and companion animals, or non-working animals, and the growing body of research showing how one can inform the other.

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In December 2021, the FACC co-sponsored “The Role of Companion Animals as Sentinels for Predicting Environmental Exposure Effects on Aging and Cancer Susceptibility in Humans,” a three-day workshop that FACC Director Rodney Page, DVM, MS, a professor of oncology at CSU, and Wendy Shelton, DVM, MPH, an FACC consultant, were instrumental in bringing to the National Academies of Science, Engineering, and Medicine in Washington, D.C.

dogs at CSU and that subsequently led to pediatric oncology trials, and it works the other way around. Many of the therapies used in dogs were first used in humans.”

“I would do anything for this dog”

R O D N EY PA G E, D VM , M S

“The idea for this workshop arose from a longstanding interest that I had in trying to shift from treatment of cancer to prevention of cancer,” Page explains. “The focus of the workshop was on laying the landscape of what the current state of the art is for aging in humans and corollary aging in companion animals, and whether types of cancer susceptibility might be related to environmental issues.” James DeGregori, PhD, CU Cancer Center deputy director and one of the featured experts at the workshop, says that while researching corollaries and similarities between cancer risk and progression in humans and companion animals is not a new field, it is one of continually growing potential and scope. “There’s a lot of overlap,” DeGregori J A M ES D EG R EG O R I , P H D says, adding that humans and dogs are at least 85% genetically identical. “We see many of the same pathways, the same genes that are mutating. There are overlaps in the types of cancer that humans and companion animals get. That’s why we’ve been able to see clinical trials that initiated in

In Molly’s case, one of those therapies was losartan, a drug commonly used to treat high blood pressure in humans. Because bone cancer commonly metastasizes to the lungs in dogs and humans, Dow and Regan theorized about using losartan to block immune system white blood cells called monocytes that promote metastasis to the lungs. STEVEN DO W, They gained approval for a canine trial, but the first several participants didn’t show improvement in their conditions. Then came Molly.

DVM, PHD

Halboth says that after Molly’s surgery, and after a biopsy showed the cancer hadn’t metastasized, Halboth still had a nagging feeling for several months that she needed to do more. “I would do anything for this dog,” she says. “Someone told me about the trial at CSU – and at this point I didn’t even know what a clinical trial was – so I took her up to Fort Collins and they told me they’d need to run some tests to see if she qualified. One of the tests showed that the cancer had metastasized to her lungs.” Molly entered the trial and began taking the drug, whose dosage researchers had increased in response to previous participants’ experiences. She was one of the first dogs to show improvement. The cancerous nodules in her lungs began shrinking, and one even disappeared. Until just a few weeks before her death in September 2018, Molly had the same boundless energy and enthusiasm for everything that came her way, Halboth says. Further response in canine study participants was significant enough that CU Cancer Center researchers at Children’s Hospital Colorado proposed the trial in pediatric bone cancer patients.

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Researching immunotherapies for human and canine cancer Another of the canine study participants who saw significant lung nodule shrinkage in the trial was Sadie, a Bernese mountain dog belonging to CU Cancer Center member Michael Verneris, MD, a professor of pediatric hematology/oncology in the CU School of Medicine. Sadie’s participation granted her an extra year beyond her cancer diagnosis and inspired Verneris to think about points of intersection between his immunotherapy research in leukemia and canine research. Dow, who leads the experimental immunotherapy research program in the FACC, began connecting with Verneris, both bringing their longtime research interests in cancer immunotherapies to the discussion. Verneris’ research uses a patient’s immune T cells, turbo-charged with proteins called chimeric antigen receptors (CARs), to seek out and destroy leukemia cells. About 85% of pediatric participants in the CAR-T study went into remission. Dow and Verneris proposed and gained approval for a trial using two oral drugs, losartan and propranolol, to make the tumor microenvironment in canine cancer patients more hospitable to CAR-T cells. The V Foundation for Cancer Research is supporting the study with funding. “Both drugs have important immunological properties in addition to their original human use,” Dow says. “These are old drugs that have been around for a long time, but 90% of the drugs we use were developed to treat humans. We just borrow from the two-legged folks to study novel uses of these drugs for our canine patients.”

Moving the needle from treating to preventing cancer Immunotherapy is one of the significant focuses of both canine and human cancer research and a primary area of overlap between the two, says Dan Gustafson, PhD, co-director of the CU Cancer Center Drug Discovery and Development Shared Resource and FACC director of research. “Osteosarcoma is a classic example,” Gustafson says. “In kids, it’s bad because it often metastasizes into the lungs, and in dogs, it’s the same but faster. A lot of research is thinking more about the biology that drives that, looking not just at tumor cells, but at the tumor microenvironment.”

DAN GUSTAFSO N, PHD

Gustafson says that in his lab, when researchers perform drug screens for canine osteosarcoma, “we also screen human cells at the same time to understand if they’re acting the same. Are we going to learn something in the dog that may be applicable in humans? As people start to understand cancer as a biological process, what we need to let the public know is that process is amplified in dogs due to their shorter lifespan. Thirty percent of dogs die of cancer, and as we treat more of them, we start understanding the parallels with humans more.”

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“In all cancer research, we’re focusing on making sure that everyone has access and everyone is represented.” Public support for research is vital, Page says, especially understanding that canine participants are patients, not animals on whom researchers are testing. Pet owners who volunteer to have their companion animals with cancer diagnoses participate in research are vital to understanding the genetic and environmental causes of cancer. Page is the principal investigator on the Golden Retriever Lifetime Study sponsored by the Morris Animal Foundation. One of the largest prospective canine health studies in the United States, it aims to identify the nutritional, environmental, lifestyle, and genetic risk factors for cancer and other diseases in dogs. The study has enrolled more than 3,000 golden retriever research participants and seen high retention. The study has already yielded a wealth of data, including blood and metabolism profiles, that are helping researchers understand environmental and genetic risk factors for cancer and begin moving the needle from treating to preventing cancer, Page says.

says. Environmental risk factors, including exposure to radon, asbestos, or cigarette smoke, have been shown to be particularly prevalent in traditionally underrepresented communities and populations, who also may have less access to veterinary and human cancer services.

Ensuring equitable participation in research

“There’s a lot we need to be doing as researchers to build relationships with these communities and to gain that trust,” Page says. “You can’t just walk in and ask for samples, so it’s a matter of making sure that everyone has equal access to the research and equal opportunity to participate in the research.”

“We have a unique resource with the Golden Retriever Lifetime Study,” DeGregori explains. “We have data not only to understand the aging process, but when they eventually pass, we’re able to look at what they die from and how many got cancers, which is a major cause of mortality for dogs.” Among the benefits of studying companion animals as sentinels for cancer progression is that “we’re living with them in the same environment, we’re hopefully getting similar exercise levels, and their lifespan is much easier to study than an entire human lifespan,” DeGregori explains. “If we’re studying these animals over time and find biomarkers for a particular exposure that leads to increased risk of a particular cancer, then we can ask if we’re seeing the same thing in human populations and try to mitigate that risk.” Companion animal and human cancer research that analyzes environmental risk factors also shows great potential to support environmental justice, Page

Companion animal cancer research that has led to similar human research, and vice versa, benefits greatly from the relationship between the FACC and the CU Cancer Center, DeGregori says. In fact, the two entities recently awarded four $50,000 pilot grants to collaborative projects between researchers at the two institutions (see Decoding Cancer, page 9).

People want to do what’s best for their companion animals Because “cancer is cancer,” Page says, and the cellular mechanisms that lead to cancer in humans also lead to cancer in companion animals, there is potential for research to include animals beyond dogs. As with all research, though, a vital aspect is not just financial support, but the willingness of participants to join studies.

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“In all cancer research, we’re focusing on making sure that everyone has access and everyone is represented,” Page says. In humans, this may include ensuring that research samples represent the whole population and that all communities and populations are equally able to join studies. In companion animals, it means working to ensure that people from underrepresented communities have equal access to enrolling their companion animals in studies, and that they’re providing study samples. As for enrolling companion animals in studies, “that’s not often a challenge,” Gustafson says. “People love their pets, and if they receive a cancer diagnosis, people want to do whatever they can for them.”

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That’s how Danielle Nau and her husband felt when their Chesapeake Bay retriever, Scout, was diagnosed with bone cancer in her left front leg in December 2019. When their veterinarian recommended amputation, they worried she wouldn’t be able to play Frisbee, climb mountains, or do other things she loved, but it was her best hope. Within four months of her surgery, she was able to do everything on three legs that she’d done on four. At a follow-up appointment in November 2020, however, Nau, who lives in Denver, learned that Scout’s osteosarcoma had spread to her lungs. After several rounds of chemotherapy that couldn’t stop the cancer from growing, her veterinarian recommended a now-completed study with FACC researchers in which canine participants with metastatic

osteosarcoma received a three-drug combination of Palladia, losartan, and propranolol. Scout completed the study in July 2021 and still takes the Palladia, Nau says, and despite her nine years still loves playing Frisbee and going on adventures with Nau, her husband, and their two young children. “She’s definitely beaten the odds,” Nau says. “January 3 was the second anniversary of her amputation, and she’s had a wonderful quality of life through the study and since it ended. It’s just amazing to think that not only has she benefitted from this research, but that someday it might help people who get an osteosarcoma diagnosis. We’re just so thankful for every extra day we’ve been able to have with her.”

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Collaborative Research Projects Highlight the Partnership Between CU Cancer Center members at CSU and Anschutz Medical Campus Four research projects conducted by CU Cancer Center members from the CU Anschutz Medical Campus and Colorado State University each have received $50,000 in pilot grant funding from the Joint Pilot Program of the CU Cancer Center and CSU Flint Animal Cancer Center. The 12-month funding promotes intercampus collaborative research, with the goal of using the research findings and results to support a subsequent multi-year national grant application. The projects represent a broad and varied spectrum of cancer research, from targeting a novel oncogene implicated in many types of human and canine cancer progression to identifying biological dependencies in canine osteosarcoma and studying similarities between human and canine sinonasal carcinoma. The pilot grant-supported projects are:

Establishing Canine Sinonasal Carcinoma as a Translational Model for Sinonasal Carcinoma Radiation and Immuno-Oncology Research Sana Karam, MD, PhD, associate professor of radiation oncology in the CU School of Medicine, and Mary-Keara Boss, DVM, PhD, assistant professor of radiation oncology at CSU, will study possible similarities between human and canine sinonasal carcinoma.

Therapeutic Targeting of Oncogenic CHD1L in Human and Canine Osteosarcoma Cell Lines Daniel LaBarbera, PhD, director of the CU Skaggs School of Pharmacy and Pharmaceutical Sciences Center for Drug Discovery, and Daniel Gustafson, PhD, co-director of the developmental therapeutics program and professor of cancer pharmacology at CSU, will research whether an inhibitor of the novel CHD1L oncogene will be an effective therapy alone or in combination with other drugs in treating human and canine osteosarcoma, and determine dose response for the CHD1L inhibitor.

Identifying Biological Dependencies in Canine Osteosarcoma Using Whole Genome CRISPR-CAS9 Libraries Molishree Joshi, PhD, pharmacology instructor in the CU School of Medicine, James Costello, PhD, associate professor of pharmacology in the CU School of Medicine, and Dawn Duval, PhD, associate professor of clinical sciences at CSU, will work to identify essential genetic drivers in a panel of canine osteosarcoma cell lines using whole genome CRISPR-Cas9 screening.

A One Health Approach to Supporting Breast Cancer Survivors and Their Companion Animals Linda Cook, PhD, associate director for population sciences in the CU Cancer Center, Jennifer Currin-McCulloch, PhD, LSW, assistant professor of social work at CSU, and Lori Kogan, PhD, professor of clinical sciences at CSU, will address the hypothesis that breast cancer survivors garner benefits from their companion animals while also experiencing stress related to their animals’ wellness and decisions about the animals’ future.

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CLINICAL

CARE

Helping Women Understand Well-Being Outcomes After Surgery CU Cancer Center member Sarah Tevis, MD, aims to develop a decision aid for women who receive a breast cancer diagnosis. By Rachel Sauer When a woman receives a breast cancer diagnosis, she may have many questions about her immediate future — the stage of the disease, what treatment she’ll receive, where it will happen. In the longer term, though, the questions become much more difficult to answer: Will I feel accepting of my body? Will I be sexually confident? Will I experience a lot of pain? These are questions University of Colorado Cancer Center member Sarah Tevis, MD, an assistant professor of surgical oncology, is aiming to help women diagnosed with breast cancer to answer. Since 2019, she and her multidisciplinary co-researchers have surveyed women diagnosed with breast cancer to better understand quality-of-life outcomes. In a study published in October in the Annals of Surgical Oncology, her team presents data gathered from 3- and 6-month reported outcomes from patients who had lumpectomies and mastectomies. A major goal of the research, Tevis says, is to develop decision-making tools to help women newly diagnosed with breast cancer understand what they might experience in the long term after diagnosis “We’re hoping to collate a large group of patient data to get a sense of what the average patient experiences three months, six months, a year after treatment,” Tevis explains. “It gives us a foundation of data to be able to tell patients, ‘Here’s what other people in situations similar to yours have experienced.’

For example, participants were asked to rank, on a one-to-five scale, how often in the past week they felt confident in a social setting, of equal worth to other women, and attractive. They also rated their satisfaction with the information they received from their health care providers.

“We’ve been really good about telling patients what to expect short-term, maybe in that first month after surgery, but beyond that we haven’t been able to give them good, data-based information on how they might feel one year after surgery or even more long term.”

The data were compared between patients who had lumpectomies and mastectomies at pre-operative baseline, and at three months and six months postoperatively. Overall, Tevis says, patients who underwent lumpectomies reported greater breast satisfaction, psychosocial well-being, and sexual well-being over time than those who underwent mastectomies, though both groups reported a decline in physical well-being over the short term.

Asking patients to consider areas of well-being

Tevis and her co-researchers began their research by asking patients who received a breast cancer diagnosis to complete the BREAST-Q survey, a validated survey tool measuring quality-of-life outcomes. The survey asks women who have undergone or are currently undergoing treatment for breast cancer to quantify their experiences in areas such as psychosocial well-being, physical well-being, and sexual well-being, among others.

S A R A H T EVI S, MD

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One of the significant findings is that even preoperatively, sexual health registered lowest among the areas of well-being in which women were surveyed, Tevis says. She and her co-researchers have followed up these findings by asking 80 women to complete a sexual health symptoms survey.

“We felt that if women are already starting off with low scores in this area, treatment is only going to make it worse,” she says. These findings have led to a partnership with Catch it in Time, an arts-focused nonprofit dedicated to early detection of cancer. The aim of this collaboration is to create a series of videos, currently in development, featuring women who have undergone treatment for breast cancer discussing their experiences with sexual health during and after treatment. The videos also will feature providers and experts in the field who will offer mitigation strategies and resources for women who are experiencing symptoms. “We want to normalize the symptoms that women are having, so I think having patients in the videos is going to be really impactful,” Tevis explains. “They’re sharing their experiences and offering up suggestions for things women can try if they’re having certain symptoms, giving them an idea of when they should reach out for more support and more resources.” Tevis says she initially worried that many women would hesitate to complete a sexual health survey or participate in focus groups, “but a lot of women were saying they wanted to learn more about this, and they were glad to participate because they wanted the information and to help other patients.”

Providing patients with more supportive services

The data gathered from patient-reported outcomes at baseline, three months, and six months is an important step in an ongoing research process to create more specific, long-term decision aids for people diagnosed with breast cancer, Tevis says. A next step is to report data for outcomes at one year, as well as to gather enough data that patient averages can more specifically represent an individual’s demographic. “Developing this decision aid has the potential to help patients make really

well-informed decisions and get a better sense of what they might expect short and long term after treatment,” Tevis says. “We want to help them better understand how they might feel after surgery and to have the resources they need. “Continuing this research and these projects, we’re working to provide more supportive services for patients. We’re still in the early stages of developing a decision aid, but with these data we can look at all these different areas and figure out where we can provide more supportive services.”

“Continuing this research and these projects, we’re working to provide more supportive services for patients.”

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Addressing the International Childhood Cancer Crisis CU Cancer Center investigator Sandra Luna-Fineman, MD, helped create a WHO framework for fighting childhood cancer around the world. By Greg Glasgow Sandra Luna-Fineman, MD, treats children and adolescents with cancer from around the U.S. in her role as a pediatric oncologist at Children’s Hospital Colorado, but she knows that children in low- and middle-income countries around the world need her help the most. In 1999, Luna-Fineman — now a University of Colorado Cancer Center investigator and an associate professor in the CU School of Medicine — helped establish a pediatric cancer center in her native Guatemala; later, as a consultant with St. Jude’s Children’s Hospital, she developed the retinoblastoma and Hodgkin committees and treatment modules for the Central American Pediatric Hematology/Oncology Association and helped establish multidisciplinary care guidelines and practices for childhood cancer in Central America, the Dominican Republic, and Haiti. As part of her latest effort to increase survivorship of childhood cancers in low- and middle-income countries, Luna-Fineman spent the past two years helping to create the Global Initiative for Childhood Cancer (GICC), a World Health Organization (WHO) framework for fighting childhood cancer. The 126-page document lays out the troubling statistics — more than 10,000 children are diagnosed with cancer each day, and the survival rate is between 15% and 45% in low- and middle-income countries, as opposed to 80% in high-income countries — as well as the reasons for the inequity and what policymakers in those countries can do to implement childhood cancer services.

Explaining inequities and challenges “There are several reasons for the inequity,” Luna-Fineman says. “One is late diagnosis, or lack of diagnosis. A lot of these countries don’t have the infrastructure for services like pathology, radiology, or radiation therapy. So if early diagnosis cannot be done, how do you implement childhood cancer services in a low- or middle-income country? You have to start little by little, and as a center or country gets more sophisticated, they can improve pathology, improve imaging, improve the complexity of treatment used.”

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A distinctive challenge of childhood cancers, LunaFineman says, is that they are rare and most often start in very immature cells, meaning there is no known environmental or behavioral cause and no way to prevent them, as can be done in adult cancer. Also, childhood cancers are very different from those in adulthood. “To give you an example, colon cancer has many mutated genes, while most childhood cancers have a small number of genetic abnormalities that cause the cancer,” she says.

A CUREAll to cure all The WHO’s “CUREAll” framework for fighting childhood cancer looks to increase the capacity of countries to provide quality services for children with cancer and to increase prioritization of childhood cancer at the global and national levels. CUREAll is an acronym emphasizing the importance of Centers of excellence; Universal health coverage; Regimens and standards of care; and Evaluation and monitoring, all supported by Advocacy, Leveraging financial assistance to help families through treatment, and Linked governance. The document Luna-Fineman helped to create is a guide for policymakers on how to institute the framework in their own countries. “I’m not a public health person; what I am is a pediatric oncologist with a lot of knowledge of how it’s done, and what works and what doesn’t work,” Luna-Fineman says. “I was charged with creating a document that shows what really needs to be done in the country to be able to push this forward.” The WHO chose six “tracer cancers” for implementing programs and monitoring progress in childhood cancers worldwide, and the document lays out the justification for the selection of each: acute lymphoblastic leukemia because it is the most common childhood cancer, for instance; retinoblastoma because it combines specialties to partner on early diagnosis.

“Ophthalmologists have to work with the oncologist on how to address the eye tumor, diagnosing early to save lives, save vision, and save eyes,” Luna-Fineman says. “The reason we chose these six index cancers is because not only are they very curable without complex therapy, but focusing on these actually will make the local medical and paramedical teams grow in a way that they can, later on, treat other types of childhood cancer.” The other tracer cancers are Burkitt lymphoma, Hodgkin lymphoma, Wilms tumor, and low-grade glioma.

Changing the face of childhood cancer The document also addresses the importance of psychosocial support, education, and nutrition when it comes to surviving and living with childhood cancers, as well as the social, emotional, and economic impacts of childhood cancer on the families. It includes guidelines on implementing the CUREAll framework, including such steps as assessment, planning, and monitoring.

S A N D R A L U N A- FI NEMAN, MD

“Now that this is written, we can give it to policymakers in each country: ‘Here is how you do it; if you need help, we want to help you,’” Luna-Fineman says. “The WHO can offer help to most countries, forming partnerships to train medical providers, nurses, pathologists, radiation therapists, and so forth. “This is going to change the face of childhood cancer,” she continues. “We have 28 countries that are already running the WHO GICC, using the CUREAll framework. By the end of 2022 we’ll have 50, and by the end of 2023 we’ll have 100 countries participating. The aim is that by 2030, 60% of all kids around the world are surviving childhood cancer.”

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The opportunity to grow older Connie Walters found new hope for her lung cancer thanks to CU Cancer Center research on an unlikely marker that allows them to prescribe a drug with long-term benefits. By Rachel Sauer At her lowest point, after hearing there wasn’t much more that medicine or science could do for her, Connie Walters asked her best friend and ex-husband, Abel, to stay with her overnight. She wasn’t sure she would wake up, and she didn’t want to die alone. A part of her was ashamed she had lung cancer and embarrassed to admit her diagnosis to anyone because “a lot of

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times people want to say something negative or ask what you did to get it. If you smoked, there’s this sense that you deserve it. “I smoked for 40 years, and even though I quit the day I got diagnosed, there were times I’d think I brought this on myself. People would say, ‘Don’t be like Connie,’ and that made me feel really ashamed.”

After three rounds of chemotherapy beginning in June 2012, Walter had reached a point of resignation. She was coming close to accepting what felt like the inevitable end of her life. However, in one final attempt to help, her oncologist referred her to University of Colorado Cancer Center member Ross Camidge, MD, PhD, a professor of medical oncology.

the benefit of the doubt.’ The fact that she tested positive for the ALK change is one of the reasons why we shouldn’t let prejudices interfere with who we do tests on.”

Receiving a lung cancer diagnosis

For a long time, Walters didn’t have time to slow down and think about how it was getting harder and harder to catch her breath. For decades she was the lady at Denver International Airport who wore a variety of hats, from working in accounts for the companies that operated the airport’s restaurants and bars to repairing cash registers and leading training in customer service.

“It’s important that we treat every patient without judgment.”

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Camidge and the multidisciplinary team that accepted Walters as a patient decided to perform another biopsy to get a bigger sample of the dominant mass in her right lung. Markers of specific mutations or other genetic changes driving some lung cancers have transitioned the care of advanced lung cancer in recent years. However, most of these tend to occur among those who get lung cancer and have never smoked. Testing on Walters’ previous biopsy had not shown any of these specific markers, but the sample they tested had been very small. “We wondered if something had been missed, so we thought it was worth another look,” Camidge says. Results from the new biopsy showed that Walters’ cancer was ALK positive. Her cancer cells had acquired a break in the anaplastic lymphoma kinase gene. She had not been born with it, but this new change in some of her cells would turn out to be the ringleader of her particular cancer. ALK positivity is rare in lung cancer in general — it is seen in one of every 20 cases — but it is even more rare to find it in someone with a significant smoking history. “When ALK was first discovered in the late 2000s, some big cancer centers advocated to only test for it in people with lung cancer who had never smoked. We ignored that approach from the start,” Camidge explains. “It’s important that we treat every patient without judgment. With Connie, we did not want to judge a book by its cover. We just said, ‘Let’s give her

She was raising a son and a daughter — Brandon and Autumn, both now adults — and setting up her own cash register repair business while being on 24-hour call for repairs at the airport. She was one of just a few women in Colorado who repaired cash registers. It was busy and high-stress, but she enjoyed the work and the financial independence it allowed her and her family. Through the first months of 2012, though, she noticed it was getting more and more difficult to walk the airport’s long hallways and concourses. It got to the point that she was having to pause every so often and pant for air, so she scheduled an appointment with her doctor. She tried not to think about it, but in the back of her mind was a constant reminder that her sister, Debbie, had died at age 47 of lung cancer that migrated to her bones and brain, and that her mother was also battling cancer. Walters had always been a positive thinker, so she tried to keep her mind from going to negative places. But the first biopsy revealed the news she didn’t want: She had lung cancer. “I was in shock, despite my family history,” she said. “My whole world kind of stopped. I forgot about the airport, I forgot about fixing registers, I forgot about accounting and data input, my phone ringing nonstop. I gave notice at work because I knew I had to focus on me and on getting better, but part of me thought my life was over.” Between June 2012 and July 2013, she had three rounds of chemotherapy that exhausted her, caused her to gain a lot of weight, and left her feeling bruised and broken. She felt miles away from the woman who had done every workout with Richard Simmons during her 2003 Caribbean cruise vacation with her mother. She ended up feeling as though the physical and emotional toll had been for nothing, because the chemotherapy couldn’t kill all the cancer. Her previous oncologist, who also treated her mother, had taken Walters’ treatment as far as he could, but he gave her Camidge’s card as one of the last things he could do to help her.

Testing for ALK “When you first meet Connie, what you notice right away is that she’s the most positive person,” Camidge says. “One of the things I really

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like about working with people with cancer is when they’re first diagnosed, the relationship is more oneway, more about what we’re going to do for them. But over time there’s a shift in that, and it becomes more two-way. I get an enormous amount out of interacting with Connie. She makes my day better, she makes all my staff happy, she gives as much to us as we have to her.” The ALK-positive marker in Walters’ cancer had only been described in lung cancer a few years previously. Fortunately, the CU team had been involved in the trials that led to the first targeted drugs for treating this subtype of the disease. Because of that involvement, testing for ALK positivity had been part of the cancer center’s routine practice for its patients since 2009. Walters started on Crizotinib, the first licensed ALK inhibitor, which had only been approved by the Food and Drug Administration in 2011.

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“I knew that this was kind of a ‘magic pill,’ but they might have hesitated to give it to me because they thought I was on death’s door,” Connie recalls. “I tried my best not to be on death’s door, I tried to sit up straight and have some energy, but I was so sick. “Dr. Camidge knew I was very ill, but he gave me this pill anyway — they call it a miracle pill — and it brings people back to life who are dying of lung cancer. It brought me back to life, and I was like, ‘Oh, my God, I’m alive again, I can function again.’ I was so happy and so thankful to Dr. Camidge for that.” A few years later, however, one of the problems with Crizotinib emerged: It couldn’t stop the cancer from getting into Walters’ brain. Even though the rest of her body was responding beautifully to the drug, she developed about 10 sites in her brain that required focused radiation in June 2015. Three months later, she joined a clinical trial for another, now-approved ALK inhibitor drug called Lorlatonib and has taken it ever since with occasional adjustments to the dose.

“Our approach is to understand both you and your cancer.” “There’s always a reason to be happy”

“The ideal goals of treatment for lung cancer are to achieve perfect control of cancer and perfect quality of life,” Camidge says. “It doesn’t matter whether we achieve it or not, that’s what we’re aiming for. So it’s not always ‘no pain, no gain.’ Our approach is to understand both you and your cancer. If we are controlling it, our job is also to manage all the other health issues in your life so you can be a friend and a mother and a companion. We want to give people the opportunity to grow older.” Walters, now 62, laughs that she’s gained years she thought she wouldn’t have, and with them the various maladies of growing older. She developed diabetes and is working to manage it, as well as other conditions that have limited her mobility if not her positive attitude. “Each day is a gift,” she says. “I have Autumn and my (6-year-old) grandson here with me, and Abel comes every day. I feel blessed that I have my home and I get to be with the people I love. There was a point when I thought I wouldn’t get any of this, when they told me it was hopeless, but I’m still here. There’s always a reason to be happy.”

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WELLS MESSERSMITH, MD,

TAKES ON NEW LEADERSHIP ROLE AT UCHEALTH BY GREG GLASGOW

The CU Cancer Center member also was named associate director for clinical services at the cancer center.

In January, University of Colorado Cancer Center leader Wells Messersmith, MD, was named chief medical officer of oncology services at UCHealth. In his new role, Messersmith oversees cancer care at all UCHealth locations with a focus on expanding advanced treatments and the clinical trials UCHealth offers in partnership with the CU Cancer Center. Messersmith also was recently named associate director for clinical services at the CU Cancer Center; he previously served as associate director of translational research. He will continue to hold his position as division head for medical oncology. We spoke with Messersmith about his journey into medicine and his new role.

Q: What made you want to go to medical school? W ELLS MESSERSMI TH, MD

A: I thought I was going to be a PhD in biology or biochemistry. I just happened to take enough courses to qualify for medical school, and I said, “I’ll just take the MCAT entrance exam to keep my options open.” I shadowed various doctors during my undergraduate years and decided that I loved the intersection between science and taking care of people, so I chose medical school.

Q: Why did you decide to focus on cancer specifically?

A: I had actually applied to a fellowship in general medicine, then I did a rotation in GI cancer when I was a medicine resident, and I just fell in love with it. I love the multidisciplinary aspects and the impact you have on people’s lives. An oncologist is really a primary care doctor, but for a cancer patient. You’re responsible for everything; you’re not just

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focused on one organ or problem. And you’re alongside someone during some of the toughest things they’ll go through. It’s often challenging, but I also find it really rewarding. I’ve also found that because of my research emphasis, I always have a sense of optimism and hope. You can see what’s coming down the pike with new advances in detection and treatment, and there have been such exciting changes in cancer care. It helps keep you balanced, so that you can keep that empathy and that compassion with patient care.

Q: What is the focus of your research?

A: I look at tumor samples and tumor models to figure out which investigational therapies will work and which won’t, and how we can personalize these therapies. I’m essentially doing clinical trials in the lab prior to doing a clinical trial with patients, looking for effective combinations and markers of drug susceptibility. I also do a fair number of phase I trials, or first-in-human studies. That’s been a real pleasure for me, because we’ve gone from developing what we call cytotoxic drugs, which are basically poison drugs — they kill dividing cells, and you lose your hair, and your blood counts go down — to studying immune therapies that are much less toxic to people outside of overstimulating the immune system. That has been wonderful to see. The cost/benefit proposition for patients is so much higher than it used to be, since modern drugs are often less toxic and more efficacious.

Q: What brought you to the University of Colorado Cancer Center?

A: I came here because I loved the idea of building a program. Back in 2007, there really wasn’t much of a specialized GI cancer program in medical oncology. I was recruited here to build one, and it’s been amazing to see how it grew. Together with multiple other specialties, we were able to create multidisciplinary clinics and really increase our efforts in terms of clinical trials and options for patients. When I first got here, it was sad to see that so many people from Denver had to travel to other cities to get expert cancer care. But nowadays, you don’t have to leave Colorado to get access to cuttingedge trials, multidisciplinary care, and highly specialized, expert care. That’s important, because it’s really difficult to leave your family or support system to get care in a different city.

Q: Do you have any personal experiences with cancer?

A: My brother was diagnosed with leukemia after I moved to Denver. Having a family member go through a bone marrow transplant really teaches you what the experience is like on the other side. That got me even more interested in what the patient and their family go through, and the challenges they deal with. Fortunately, my brother was cured, but it was a long, difficult road for him. I think that made me a more empathetic physician, because you see what it’s like for the patient and family.

Q: What are you most excited about in your new role at UCHealth?

A: My big-picture view is that people across the Rocky Mountain region should have access to top-quality care, yet get as much of that care as they can close to home. That includes specialization, multidisciplinary care, and access to clinical trials. We can’t do all three of those at every community clinic,

but my job is to look at how we can integrate our care so that patients have access to these things, and yet do as much locally as we can. We have satellite centers in Lone Tree, Cherry Creek, and Highlands Ranch, so we can tell patients, “Why don’t you go to your home clinic and get four months of chemotherapy, then come back for your highly specialized surgery?” Increasingly, we can even perform complex cancer surgeries at Highlands Ranch. At these smaller clinics, everyone knows each other by name; you’re always being seen by the same people. That community feel is highly valued by patients. At the same time, the physicians, patients, and community have access to this large academic medical machine for those episodes of care that must be specialized, or even just to ask advice. It’s the best of both worlds.

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Living in the Light Endowment established in memory of multiple myeloma patient Mary Jo Dougherty supports research working toward a cure for the cancer. By Rachel Sauer Michael Joseph Roark — Mike to his friends — met Mary Jo Dougherty in a ski fitness class at the International Athletic Club in downtown Denver. This was before specialized fitness platforms, so the training happened on wooden benches. Dougherty was sharing one with some other guy, “and I kind of nudged him out so I could be with Mary Jo,” Roark remembers. “Afterward, I asked her if she’d like to get a drink. She hesitated, so I said, ‘Oh, just say yes.’” Yes is such a small word, but it’s one Dougherty didn’t hesitate to use: yes to adventure, yes to exploration and new horizons, yes to life as big as she could live it. She said yes to that drink, and decades later, their license plate read “MJSKIMJ” – Michael Joe + Mary Jo Ski Mary Jane, their favorite ski area. There’s so much Roark can say about the incredible woman he married — her devotion to her three stepchildren and two grandchildren, her determination, her embodiment of a “work hard, play hard” life ethos, her wide-open heart and boundless capacity for love — that he almost doesn’t know where to begin. So maybe the place to start is on the bench at the Denver Botanic Gardens — a spot

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she dearly loved — that was placed in her honor after she died in October 2019, following a sixyear battle with multiple myeloma. A plaque on the bench reads “Live in the light,” because that’s what she did. To further honor the woman he loved for so long, Roark established the Mary Jo Dougherty Endowed Fund for Multiple Myeloma Research at the University of Colorado Cancer Center with the goal of supporting research working toward a cure for the disease Dougherty never allowed to defeat her. “She was determined not to let it mess up her life,” Roark says. “The more I thought about it, the more I wanted to continue to honor her memory by doing what I can to fight this horrible disease.”

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OUTDOOR ADVENTURES WITH HER FAMILY Anyone who knew Dougherty knew that she felt just as at home on a double black diamond ski run or in a field of moguls as she did walking down the sidewalk of her neighborhood. A lifelong athlete, she earned a swimming scholarship to the then-Western State College in Gunnison, where she also played soccer. She skied and hiked, summiting almost all of Colorado’s fourteeners, and when she met Roark she was introduced to windsurfing and mountain biking. The whole family — including Roark’s two sons and daughter from his previous marriage — relished those outdoor adventures together. Dougherty’s stepdaughter, Michelle Roark, was even a two-time Olympian in women’s moguls, as well as an award-winning competitor in the U.S., World Cup, and World Championships. “We traveled around Europe and North America to watch Michelle ski,” Roark says. “Mary Jo loved to travel. Her brother ran an American school in Italy for 11 years, so we visited him there

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“The more I thought about it, the more I wanted to continue to honor her memory by doing what I can to fight this horrible disease.”

frequently and always had to detour through Paris because that was her favorite city in the world.” Dougherty’s determination and drive were evident not only in her athletic prowess, but professionally. Beginning her career as a paralegal, she pursued her Juris Doctor degree at night, graduating cum laude from the University of Denver. She became an attorney and developed special districts throughout Colorado.

AN UNEXPECTED DIAGNOSIS Dougherty had always been able to push herself and count on her body to do what she needed it to, so it was a surprise when, in early 2013, she was doing a clean-andjerk during a weightlifting class and suddenly her back felt terrible. Visits to the chiropractor and massages didn’t help, and while climbing Mount Oxford on July 4 that year, she had to ask Roark to carry her pack. “That was really unusual,” Roark recalls. “Then we were up in Hood River (Oregon) to windsurf the Columbia River Gorge and were mountain biking on a non-windy day, and she had to turn around and go back. When I got back, she had tripped over a root and could hardly walk.” After returning home to Denver, a series of scans with a sports medicine physician at UCHealth University of Colorado Hospital led to an agonizing phone call. “She called me and said, ‘Honey, I’ve got one of three different types of cancer,’” Roark recalls. “I said, ‘What? That can’t be right! Didn’t you tell her you just tripped?’ But we learned it was either leukemia, lymphoma, or multiple myeloma.”

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Soon after, Dougherty met with Clay Smith, MD, a professor of hematology in the CU School of Medicine and director of the UCHealth Blood Disorders and Cell Therapies Center. “When I met with her, CLAY SMI TH, MD she said she had some back pain, but then I looked at her scans and one of the bones in her back was completely gone,” Smith says. “I have no idea how she was even sitting there talking to me, with what she described as a little bit of pain.” She was swiftly admitted to the hospital and soon received a diagnosis of multiple myeloma, a type of cancer that begins in plasma cells. The cancer had destroyed her L3 vertebra and attacked her L4 and L5, so she had surgery to fuse them before she could undergo stem cell harvesting followed by chemotherapy.

“HER MAGIC WAS HER PERSONALITY” Over the following years, Dougherty had temporary successes with stem cell transplant, chemotherapy, immunotherapy, and other treatments, but she inevitably experienced recurrences of the cancer. However, she was determined to continue living the life she wanted, and to support the research that will one day defeat the cancer she lived with for six years.

She became an active fundraiser for the Leukemia & Lymphoma Society and in 2017 was named the organization’s Woman of the Year for raising $239,000, shattering previous fundraising records for the Rocky Mountain region. “Her magic was her personality,” Roark says. “She was such a warm and caring person and people couldn’t say no to her. You couldn’t not like her.” Through her cancer journey, she continued doing the things she loved — skiing with her grandchildren, biking, and windsurfing — even though it was against the initial advice of her doctor. “She would get her treatments and then she would go windsurfing,” Smith recalls with a laugh. “The first few years I was like, ‘You know, Mary Jo, you shouldn’t do this, you shouldn’t do that.’ And she would just smile at me and go off and do what she wanted, then come back and show me pictures. And in those pictures she was smiling ear to ear. She taught me a really important lesson about being a doctor, that just to live timewise is not enough for a lot of people. They want to live well.”

LIVING THE LIFE SHE WANTED Until the last few months of her life, when treatments were no longer working, Dougherty continued to do the things she loved with the people she loved. When it was obvious there was nothing more medicine could do for her, “Mike and I were in tears and kind of a mess,” Smith says. “Just to show you how indomitable and

strong she was, she told us, ‘You guys will be OK, I’ll take care of everything.’ I don’t know how she even got out of bed then, but she did and gave me a hug that I’ll remember for the rest of my life. Even at the very end, she was just the strongest person and she was looking after her doctor and her husband.” It’s in Dougherty’s memory and in her honor that Smith currently is raising funds for the Leukemia and Lymphoma Society’s Man & Woman of the Year Campaign, a philanthropic competition to support blood cancer research. “For those six years she lived with myeloma, she lived the life she wanted,” Roark says. That life included skiing moguls, taking her two young grandchildren to high tea at the Brown Palace hotel in downtown Denver, and visiting all the vistas and secret spots she loved. It’s in several of those spots that the people who love her have placed small memorials in her honor — a bench or a plaque on a tree to mark that spot as cherished by a glorious woman who wove her life out of light and love, and who drew her family and friends into its glow. “How do you describe a woman like Mary Jo?” Roark says. “There aren’t enough accolades in the English language.”

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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 Greg Glasgow | Gregory.Glasgow@cuanschutz.edu Design: Candice Peters | Design & Print 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: coloradocancercenter.org 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.

Celebrating Our NCI Renewal T H E

FROM THE DIRECTOR RICHARD SCHULICK, MD, MBA DIRECTOR, UNIVERSITY OF COLORADO CANCER CENTER ARAGÓN/GONZALEZ-GUÍSTÍ ENDOWED CHAIR OF SURGERY, UNIVERSITY OF COLORADO SCHOOL OF MEDICINE

Comprehensive Cancer Center A Cancer Center Designated by the National Cancer Institute

We want to make sure that everyone in the state has equal access to cancer prevention and treatment.

M E S S A G E

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In March, we got the great news that the National Cancer Institute (NCI) has officially renewed the University of Colorado Cancer Center’s status as an NCI-designated comprehensive cancer center, which means we meet rigorous standards for transdisciplinary, state-of-the-art research focused on developing new and better approaches to preventing, diagnosing, and treating cancer. The CU Cancer Center is one of just 52 NCI-designated comprehensive cancer centers in the country, and the only such institution headquartered in Colorado. This is a redesignation that takes place every five years by nationally recognized peer reviewers. It allows us to receive NCI funding that helps us continue to work toward our mission of preventing and conquering cancer. We have held this prestigious title since 1997. The CU Cancer Center has contributed so much in terms of the knowledge of cancer, the prevention of cancer, the education of the Colorado public about cancer and cancer prevention, new therapies, and better ways of taking care of cancer patients. After they’re cured of cancer, former cancer patients still need a lot of follow-up and support. That’s another area of focus for our researchers and providers. The NCI renewal specifically recognizes our efforts in prevention and awareness of cancer, basic science and translational research, education, and community outreach and engagement — particularly to people in underserved communities and rural areas in Colorado.

Other factors that make the CU Cancer Center special are our multidisciplinary clinics — in which a team including specialists from different areas comes together to discuss the best treatment plan for the patient — and our focus on diversity, equity, and inclusion. If you have leadership and membership that reflects the community you serve, you can care for them better. We are also increasing our efforts in diversity, equity, and inclusion to make sure all the citizens of Colorado and surrounding states have excellent access to our cutting-edge clinical trials and that we are training and promoting a more diverse workforce. The NCI renewal process is rigorous and takes a lot of time to go through, but it makes it all worth it to once again be named an NCI-designated comprehensive cancer center. It’s confirmation of the research we conduct and the care we provide. We are here to prevent and fight cancer and to help those diagnosed with cancer beat the disease and lead full, happy lives.