Collaborating to Conquer Cancer: C3 Winter 2016

C O L L A B O R AT I N G

T O

C O N Q U E R

C A N C E R

WI NTER 2016

DOES YOUR GUT HOLD THE KEY TO CANCER ?

04: CANCER AND THE MICROBIOME 12: NO PLANS BUT LIFE ITSELF 10: Q&A WITH THOMAS R. CECH, PhD 11: C3 MD MANALI KAMDAR, MD 16: STRONG IS THE NEW HEALTHY

ANSCHUTZ MEDICAL CAMPUS

N3WS TAY LOR ABARC A

CANCER NEVER SLOWED ME DOWN: SCOTT’S STORY Scott Monserud, sports editor for The Denver Post, has been active all his life. He played sports of all

D O U B L E N E G AT I V E L E A D S TO B I G P O S I T I V E A G A I N S T B L A D D E R C A N C E R M E TA S TA S I S

kinds growing up with five older siblings on a farm.

So when he suddenly felt extreme fatigue and lower

A paper stemming from a long-

back pain a year ago, Scott knew something was

standing collaboration between

not right. But he wasn’t expecting the diagnosis

investigators at the University of

of stage IV metastatic prostate cancer.

Colorado Cancer Center and Yale,

“I was devastated, and terrified,” Monserud

Cell, demonstrates a “double

to the urologist that I might have cancer but was

negative” strategy that bladder

not ready to be told it had spread outside

cancer uses to proliferate, turning

my prostate.”

off the cancer-suppressing gene

While undergoing chemotherapy, Scott sought MONSER UD WI TH A S U PPORT IV E F R IE N D

published in the journal Cancer

said. “I had prepared myself mentally before going

RhoDGI2 that is supposed to turn

THEO DO RESCU

second opinions from experts at the University of

off cancer. New understanding of this mechanism

Colorado Anschutz Medical Campus in Aurora. He

may allow doctors to add one more negative,

was put in touch with E. David Crawford, a surgeon, who recommended he have cryotherapy surgery after

stopping bladder cancer’s ability to stop the

he was done with his chemotherapy. The purpose of the surgery is to destroy cancer cells in the prostate

tumor-suppressing gene RhoDGI2, thus letting

by freezing them with extremely cold liquid nitrogen or argon gas.

the gene do its job of fighting cancer.

The day after returning from the Super Bowl in California where he directed The Denver Post’s coverage

Basically, loss of RhoDGI2 leads to increase in

of the Denver Broncos’ victory over Carolina, Scott received cryotherapy surgery at CU Cancer Center.

an enzyme called osteopontin which then jump-

Now his PSA is in the normal level and his bone scans are promising.

starts the ability of cancer cells to act as seeds

“My advice for anyone going through a similar situation would be to try not to panic and assess all of

of a new tumor site. Osteopontin expression is

your options. Finally, try to stay positive and work to improve your diet. Attempt to exercise and lift weights.

associated with poor outcomes in human bladder

You’ll feel better and I believe it helps your body fight cancer,” Scott says.

cancer patients. When the investigators blocked this osteopontin signaling pathway in animal models, bladder cancer cells were not able to

SEARLE, KIMMEL, BECKMAN AND BOETTCHER AWARDS HELP SABRINA SPENCER

C U BOULDER

DIVE DEEP INTO CELL SIGNALING

form metastases in the lungs and lymph nodes.

“What this paper shows is that targeting this

The Kimmel Scholars Program funds 15 of the

pathway is a strong candidate for clinical therapeu-

nation’s top young cancer researchers. The

tic options,” says Dan Theodorescu, MD, PhD,

Beckman Young Investigator Program honors

director of the CU Cancer Center.

eight promising early-career faculty members. The Searle Scholar program honors 15 young faculty who have highly inventive ideas. The Boettcher Investigators program, supported by the WebbWaring Foundation, supports early-career Colorado research in the biomedical sciences. This year, CU Cancer Center investigator, Sabrina Spencer, PhD, won all four prestigious awards, validating her creative approach to studying the complex signals that can determine whether stressed and damaged cells die or survive to seed cancer. Spencer is an SPENCER

assistant professor in the CU Boulder Department of Chemistry and Biochemistry.

“Before the cells develop mutations that allow them to resist a drug, some cells have to tolerate the drug long enough to develop these mutations. We’re looking at the inception of this resistance,” Spencer says.

Specifically, Spencer studies signaling pathways that allow cancer cells to pause their growth in favor of a “survival mode” called quiescence that lets them enter a kind of cellular hibernation in the presence of drugs that might otherwise cause their death.

“Accomplishing great science isn’t just doing the obvious next step, but looking ten steps ahead.

It’s the inspiration to try crazy things,” Spencer says.

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Get more CU Cancer Center news on our blog: www.coloradocancerblogs.org.

Sign up for our bimonthly newsletter, Colorado Cancer News.

15 TO P

O F 2016

FATTY TISSUE MAY BE ‘ROBBERS CAVE’ FOR CANCER STEM CELLS, DRIVING POOR PROGNOSIS FOR OBESE PATIENTS Across many cancer types, obese patients fare worse than leaner patients. Now a University of Colorado Cancer Center study published in the journal Cell Stem Cell offers a compelling hypothesis why: Research­ers found that leukemia stem cells “hide” in fatty tissue, even transforming this tissue in ways that support their survival when challenged with chemotherapy. It is as if leukemia stem cells not only use fatty tissue as a

HEALTHLINE NAMES COLORADO CANCER BLOGS “TOP 15 OF 2016”

robbers’ cave to hide from therapy, but actively adapt this cave to their liking.

The group found that cancer stem cells in fat tissue had switched to use fatty acids as their energy source and, in fact, signaled fat to undergo a process called lipolysis, which releases fatty acids into the

Colorado Cancer Blogs is honored to be

microenvironment. When the group challenged these cells with chemotherapy, they found cells that had

included in Healthline.com’s list of the Top

switched their energy source to fatty acids were harder to kill.

Cancer Blogs of 2016. According to Healthline,

“In leukemia, the obvious niche is the bone marrow, but little attention has been paid to other sites

the award recognizes cancer websites with the

in the body. This study is one of the first to evaluate adipose tissue, fat, as a possible tumor-supporting

ability to “educate, inspire, and empower their

niche,” says Craig Jordan, PhD, Nancy Carroll Allen

readers with frequent updates and high quality

Professor of Hematology in the CU Department

information.” Additional awardees include the

of Medicine.

blog CancerWise by MD Anderson, Stand Up To Cancer, the website Cure Today by Cure

T TY FAT

Magazine, and the Well blog by The New York Times.

ISS

UE

STEM CELL

CHEMO

CU CANCER CENTER’S PAUL BUNN, JR., MD, FASCO, EARNS ASCO CU CANCER CENTER

DAVID A. KARNOFSKY MEMORIAL AWARD Paul Bunn, Jr., MD, FASCO, distinguished professor at the University of Colorado Cancer Center and James Dudley Professor of Lung Cancer Research at the University of Colorado School of Medicine has been named the 2016 David A. Karnofsky Memorial Award and Lecture recipient, a prestigious award presented at the American Society of Clinical Oncology’s (ASCO) Annual 500 PATIENTS ADVANCE CANCER

Meeting. Dr. Bunn’s distinguished career in lung cancer research includes more

CARE AT UNIVERSITY OF COLORADO

than 320 peer-reviewed articles, 200 reviews and 90 book chapters. He has

CANCER CENTER

been principal investigator on many national and local clinical trials and is the

The University of Colorado Cancer Center has

principal investigator on the NCI’s CU Cancer Center SPORE grant in lung

enrolled 500 patients in a unique research col-

cancer, designed to speed the progress of new treatments from basic research

laboration with partners in the Oncology Research

to clinical use. Dr. Bunn served as ASCO President from 2002 to 2003, as

Information Exchange Network, or ORIEN. The

president and CEO of the International Association for the Study of Lung Cancer, chairman of the FDA

study aims to improve cancer care by gathering

Oncology Drug Advisory Committee, and is the founding director of the CU Cancer Center.

data from patients with various kinds of cancers

BUNN

“I view this award as an honor but also as an indication of progress in the field of lung cancer,” Bunn

over the course of their treatment to match them

says. “In the last decade, molecular therapies and immunotherapies have improved outcomes for lung

with the best treatment options.

cancer patients considerably. New screening protocols and methods have reduced mortality. And getting

“One of the challenges we face in oncology is identifying which treatment is most beneficial for which patient,” said Virginia Borges, CU Cancer

people to stop smoking has made a huge impact. I view this award as a tribute to those people who made these advances in prevention, early detection, pathology, staging and treatment.”

Bunn’s career represents the branch of cancer medicine that has chosen to prioritize the science of the

Center investigator and principal investigator.

disease. Now the David A. Karnofsy Memorial Award and Lecture recognizes the impact of this approach

“This study will speed up the development of

on patients’ lives.

targeted cancer therapies and markers that can help us know with more certainty that a treatment will work.”

3 C3: WINTER 2016

CANCER and DOES YOUR GUT HOLD THE KEY TO CANCER ?

O

YO U L I V E I N

harmony O R A T L EA S T

IN D I F F E R E N CE W I T H T H E V AS T M A J O R I TY O F M I C R O O R GA N I S MS TH A T C A LL Y OU

home

.

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ctopus Springs, eight miles north of Old Faithful in Yellowstone National Park, is a bubbling pot of 91-degree, alkaline water covered in a floating film of grayish white silicate deposit called sinter. It is not home to birds or squirrels or foxes or any of the other feathered or furred creatures we associate with the park. It is, however, home to Aquifex, a pinkish-purple hydrogen-eating chemotroph that thrives in this toxic hot tub. We know this because in the 1980s, University of Colorado Boulder researcher, Norman Pace, pioneered techniques to determine what sorts of wee beasties are present in soups like Octopus Springs. Basically, he collected water with a homemade screen that looked like a furnace filter, chopped it up and compared the fragments of genetic material he found to a library of usual microbial suspects. Today Pace’s technique forms the basis for analyzing the microbes of another hot pot, namely your gut.

“Don’t poo-poo the microbiome,” says Andrea Dwyer, co-director of CU Cancer Center’s Colorado Colorectal Screening Program. Her words encapsulate the dichotomy of microbiome research: We are increasingly respecting its power even while continuing to chuckle behind our hands at the fact that it is indisputably icky and, to some, still seems like a fringe science.

Newsflash: It’s not fringe anymore. In 2012, fecal transplant became an accepted treatment for infection with the bacteria Clostridium difficile or C. diff, which releases toxins that attack the lining of the intestines leading to the condition of colitis. In 2013, the journal Nature reported that gut microbiota could influence brain activity and emotions. And further work has explored likely connections between the microbiome and conditions ranging from acne to obesity to autism to asthma to ulcers and more.

Evidence is on the rise for a role of the microbiome in another disease: cancer.

“It’s right where immunotherapy was two years ago,” says Dwyer, who, in partnership with the organizations Fight Colorectal Cancer and the Cancer Research Institute, is exploring the role of the microbiome in colorectal cancer prevention. “Based on what we’re learning, the microbiome has astounding potential. We see opportunity and we just need to drive it ahead.”

But before exploring how CU researchers are driving microbiome research, you gotta know what it is.

the Microbiome

BY GARTH SUNDEM

Have you ever thought that maybe we’re all just tiny little cells and Earth is really just a dot in the body of some giant, cosmic organism? Crazy, right? Well, it’s not so crazy to Escherichia coli. For this lovely little gram-negative, facultatively anaerobic, rod-shaped bacterium, your small intestine is the world. But E. coli is not alone in your gut. In fact, it makes up only about 0.1 percent of your “gut flora” or “gut biota” – the diverse population of single-celled creatures that call you home.

You live in harmony or at least indifference with the vast majority of these micro­ organisms. That’s for the best – the American Academy of Microbiology estimates that you may have as many as ten times the number of non-human cells in your microbiome as you have human cells in your body. In other words, you are composed of more them than you. Let’s look at this another way. The sum of your DNA codes for about 23,000 genes.

A study in the journal Protein Cell shows that the genomes of the bacteria and viruses and archaea that make up your microbiome code for about 3.3 million genes. You like to think of yourself as human, but if you define your makeup by cell type, you are more precisely a colony of over 100 trillion independent microorganisms, each with its own strategies and goals, walking around inside a container of skin that happens to be topped by a three-pound bag of neurons sentient enough to be weirded out by this paragraph.

But again, these small collaborators on your journey of life are generally helpful.

See, your 23,000 genes aren’t nearly enough to do all the things your body needs to do.

Your gut biota help to digest indigestible things and supply your body with nutrients, while defending against colonization by less good biota. The microbiota of your respiratory system and lungs protect against diseases like cystic fibrosis, asthma and chronic obstructive pulmonary disease. Microbiota of the female reproductive tract protect against infection and can affect a baby’s immune system. Through these actions, your microbiome helps to regulate your metabolism and immune system, with trickle-down effects on nutrition, disease and even the physiology of your body itself.

Basically, you can think of yourself as a project manager. There are some things you can do – actually, your genes let you do about 23,000 “things”. But there are many things you can’t do, and for all these other functions, you “hire” the expertise of your micro­ biome. Far be it from this article to make sweeping political statements about the benefits of a diverse workforce, but let’s just say that at least when it comes to your microbiome, the more kinds, the merrier. The messy balance of many microorganisms all working together, in parallel or even against each other creates a kind of beneficial white noise that your body has evolved to depend on for far-reaching aspects of your well-being.

CASEY CASS

W H A T I S THE M I CR OB I OME ?

AN D RE A D WY E R, C O . D I R EC T O R OF C U C AN C E R C E N T ER ’ S C O L O R A D O C OL ORE C TAL SC RE ENI NG P R O G R A M

“Based on what we’re learning, the microbiome has astounding potential. We see opportunity and we just need to drive it ahead.”

5 C3: WINTER 2016

FLIC KR C RE AT IVE C OMMONS / T ONY H ISGE T T

T HE “GROUND FLOOR” OF MICRO BIOME RESEARCH RESEARCH SH O W I N G MICE WITH

‘good’

M I C R O B I OM E S

resisted

CANCERS IS A TA N TA L I Z I N G C L U E.

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Imagine you had one laboratory focused on the study of the microbiome in cancer.

Now take that laboratory and chop it into pieces. Distribute those pieces among dozens of researchers in the CU School of Medicine, CU Boulder, CSU and across the UCHealth hospital system. This is what microbiome research looks like at the University of Colorado Cancer Center – dozens or even hundreds of cancer researchers are interested in the microbiome, each looking at it from the perspective of their own expertise, many exploring aspects of the microbiome through small studies undertaken as pet projects. The sum is a rich and thriving research community that with many publications and findings is driving the national conversation about the microbiome and cancer…though you’d never know it because much of this work happens under the radar, at the grassroots level of passion projects and pilot grants. In a way, the community doing microbiome research at CU is like the microbiome itself – everyone working independently with results emerging organically from the population as a whole.

If there is a central hub of cancer microbiome research at CU, it may be the lab of Daniel Frank, PhD, assistant professor in the CU School of Medicine Division of Infectious Diseases and co-director of the UC Denver Microbiome Research Consortium (MiRC). This is not because he specializes in cancer research, but simply because he is one of the campus’s one-stop shops for analysis of any microbial community.

“Give us a sample and we’ll extract the nucleic acids and characterize the population,” Frank says, adding that he has “worked with every conceivable body site.”

In fact, Frank was a postdoc in the lab of Norm Pace, the researcher whose techniques first identified the extremophile microbes of Yellowstone hotpots. Now 30 years later, Frank has been instrumental in modernizing Pace’s strategies, which he uses to power the research of collaborators studying microbial influences on conditions ranging from Crohn’s disease to colitis and even cancer.

“Right now I’m thinking about metabolism and other things. Let me switch my brain over to cancer,” Frank said on the phone. When he did, Frank told a compelling story of the microbiome in colon cancer: At the University of Michigan, researchers exposed mice to an established procedure designed to create colon cancer. As expected, some of the mice developed cancer, whereas mice treated with antibiotics did not. Then they did something special – they transplanted the microbiomes of mice that did and did not develop colon cancer into a new set of mice. In these new mice, those with “good” microbiomes resisted cancers; mice with “bad” microbiomes overwhelmingly got cancer again. “This is a tantalizing clue that the gut microbiome participates in the formation of colon cancer,” Frank says.

He, along with Vijay R. Ramakrishnan, MD, Shi-long Lu, PhD, and John I. Song, MD, recently initiated a collaborative project that will take a similar approach with oral cancer. This new team will evaluate clues in saliva samples to see if they can predict, based on microbial signatures, which patients are at most risk and thus who might receive more and less aggressive treatments.

In addition to predicting things from the microbiome, Frank and others would like to manipulate the microbiome to “affect the arc of a disease,” he says. One area he sees as especially promising is in the possibility of supportive care, “treating a dysfunctional microbiome at the same time you’re treating the underlying causes of a disease,” he says.

For example, he suggests that repairing the microbiome after cancer treatments like chemotherapy and radiation is similar to an oil company’s process of ecosystem remediation.

“After these treatments, it may be beneficial to put the ecosystem back in place,” he says.

Or, working at Children’s Hospital Colorado with medical student, Brian Nycz, and Dr. Sam Dominguez, a pediatric infectious disease specialist, Frank is exploring how manipulating the microbiome might be used to protect children from infections

PAT RIC K C AMPBE LL

following cancer treatment. “It turns out now that some of the intestinal and bloodstream infections that hit these kids may come from problems in the gut microbiome,” Frank says.

Because Frank is a cancer researcher and cancer researchers are by definition at least moderately dorky, he compares this approach to the Star Trek tricorder used

by Dr. Bones to collect comprehensive physiological data and then diagnose disease.

“Imagine a person comes in for chemotherapy and we sample the gut microbiome to predict if they will be more or less susceptible to some of these infections,” he says.

Elsewhere at the CU Cancer Center, other researchers are looking at other kinds of infections.

TH E M I C R OB I OM E I N B LOOD CANCERS D AN IE L F RAN K, P H D , A S S I S T A NT P ROF E SSOR IN TH E C U S CH O O L O F ME D IC IN E D IVISION O F I NF EC T I O U S D ISE ASE S AN D C O.D I R ECT O R O F T H E UC D E N VE R MIC ROB I O M E R ES EA R C H C ON SORTIUM, MIRC .

“Some of the intestinal and bloodstream infections post cancer treatment may come from problems in the gut microbiome”

LOZUPONE

Using a pilot grant from Golfers Against Cancer, microbiologist Catherine Lozupone, PhD, is studying whether the microbiome can affect graft-versus-host disease after bone marrow transplant for blood cancers. Basically, one strategy to combat leukemia is to erase a patient’s cancerous blood system and then regrow it using the “seeds” of a donor’s bone marrow stem cells. Unfortunately, if the donor’s blood system is mismatched with the patient’s tissue, the immune components of the new blood system can attack a patient’s tissue. This is graft-versus-host disease, or GVHD, and it can result in a chronic and even fatal combat between new blood and existing tissue. To study the possible influence of the microbiome on GVHD, Lozupone and colleagues including Vu Nguyen, MD, and biostatistics graduate student, Cuining Liu, analyzed gene sequence data from fecal samples of leukemia patients and their bone marrow donors before blood system transplant.

“We found two main things,” Lozupone says. “First, we found that leukemia patients had much less diversity of microbes in the gut – there was an overgrowth of opportunistic microbes.” However, this lack of diversity, she says, may not have been caused by or even have been contributing to the cancer itself, but may be due to the effects of chemotherapy and other treatments. That said, “Microbiome composition predicted mortality collectively from GVHD, relapse and infection,” Lozupone says. “We just don’t know if low gut diversity is only a marker of people who are sicker and sicker people don’t do as well, or if there is something in low gut biodiversity that makes people do poorer.” But sit with this a second: The diversity of your microbiome can predict whether you will succumb to leukemia or its complications.

That finding may be fairly intuitive, but Lozupone was surprised to see the same was true from the side of bone marrow donors: Donors with lower microbiome diversity were correlated with patients who went on to develop GVHD. “So a donor who had a lot of different types of microbes in their gut, their immune cells were less likely to induce GVHD in patients,” Lozupone says.

There are many ways to interpret this finding. Maybe, “If you’re a person who has many different types of microbes in your gut, your immune system might be more tolerant of another person’s system,” Lozupone says. “But even without the how and why, in addition to screening to see how well a donor’s genetics match a patient’s, seeing high diversity in a donor’s microbiome is good – and low gut diversity is a red flag.”

These findings have a handful of possible implications. “Before we use treatments like radiation and chemotherapy that pound the microbiome, maybe we will learn to take a fecal sample so that we can replace the microbiome once treatment ends,” Lozupone says (echoing Frank’s suggestion for “ecosystem remediation”). “Or perhaps there will be benefit in a fecal transplant from the same donor that is giving bone marrow – if you’re giving a donor’s immune system, maybe we should also be giving a donor’s microbiome?”

As you’ve seen, when it comes to the microbiome and cancer, there are more questions than answers. But these questions are pointing the microbiome down a promising path we’ve seen before.

C ATH E RIN E L OZ UP O NE, P H D , A S S I S T A NT P ROF E SSOR, C U SC H O O L O F M ED I C I NE D E P ARTME N T OF BIO M ED I CA L I NF O R. MATIC S AN D P E RSONA L I Z ED M ED I C I NE

“Microbiome composition predicted mortality collectively from GVHD, relapse and infection in leukemia patients.”

7 C3: WINTER 2016

PAT RIC K C AMPBE LL

T HE PROMISE OF THE MICROBIOME

TH E R E S A M E DI N A , MD, ASSISTANT PR O FE S S O R, CU S CHOOL OF MEDICINE D I V I S I O N O F M E DI CAL ONCOLOGY

“Whatever question you ask, there’s some interesting interaction or relationship you can find with the microbiome.”

T H E M I C RO B I OM E I S A N O T H ER

layer

OF H U M A N B I O L O G Y ON T O P O F THE

genome

,

WH O SE SE CRE T S AR E NO W B E I N G UN C O VE R E D.

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Theresa Medina, MD, sees the evolution of microbiome research following the same arc as research with the human genome. “Across the country, many cancer centers have created tumor banks that sequence tumors to investigate what genetic changes drive cancer growth. In addition, there are now many cancer centers across the country starting to collect information on the microbiome to see how this may interact with cancer development or improve responses to therapy,” she says.

In 2013 the National Institutes of Health completed its $115 million Human Microbiome Project. Its goal, like that of the Human Genome Project, was to establish the baseline of a healthy microbiome against which any single microbiome sample could be compared.

“There’s a huge shift toward looking at this area because it seems like whatever question you ask, there’s some interesting interaction or relationship you can find with the microbiome,” says Medina. She points to recent work combining manipulation of the microbiome with cancer immunotherapy in animal models.

If you’ve been watching cancer research, you’ve heard about immunotherapy, in which (basically) doctors attempt to teach the immune system to target cancer.

Two 2015 studies in the journal Science show that differences in the microbiome can alter a tumor’s response to immunotherapy. The findings depended on a serendipitous observation: Melanoma tumors grew faster in mice obtained from one laboratory than they did in mice from another laboratory. Why? Well, transferring the microbiome of mice with slow tumor growth to the mice with fast tumor growth was enough to slow tumor growth in this second group to the lower level. Adding anti-PDL1 or anti CTLA-4 immunotherapy to the microbiome transfer controlled tumors even better – beyond what either treatment accomplished on its own. The culprit seemed to be an abundance of Bifidobacterium and when researchers treated mice with this bacteria – a common ingredient in probiotics – they were able to improve the response to immunotherapy.

Medina also says that in addition to modulating immunotherapies, the microbiome may affect the immune system in ways that could prevent the development of cancer in the first place. “Some gut inflammation is good – the gut microbiome is influential in the development of a competent immune system,” she says. “But we’ve seen that alterations in the microbiome are associated with the development of some cancers, especially colorectal cancer.”

Immune regulation isn’t the only way the microbiome may affect cancer. “I also wonder whether the microbiome may affect metabolism in a way that helps to decide how quickly and how efficiently cancer is able to use energy to power its growth,” Medina says. Still another way the microbiome could affect cancer development is through its influence on the “virome” – the population of viruses in the human body.

“For example, the microbiome may help to determine if infection with HPV leads to cervical or head-and-neck cancer,” Medina says.

“With the microbiome, we’re at the ground floor of understanding,” says Dan Frank.

“What is safe and what is effective have largely yet to be determined.” But we know enough to know there’s more there. The microbiome is, as Frank might point out, a new frontier – another layer of human biology on top of the genome, whose secrets are just now being uncovered. And like our understanding of the genome has allowed us to make quantum leaps in our understanding and treatment of diseases, unpacking the details of how we coexist, cooperate and compete with our microbiome may allow us to take the next giant leap in cancer treatment.

DEC DINGCANCER Increasing evidence indicates a key role for the bacterial microbiota in carcinogenesis.

Schwabe, Robert F. and Christian Jobin.

“The Microbiome and Cancer”. Nature Reviews Cancer 13.11 (2013): 800-812.

Changes in the gut microbiome … directly contribute to tumorigenesis and suggest that interventions affecting the composition of the micro­ biome may be a strategy to prevent the development of colon cancer.

Zackular, J. P. et al. “The Gut Microbiome Modulates Colon Tumorigenesis”. mBio 4.6 (2013): e00692-13-e00692-13.

The trajectory of where the current work is headed suggests … that microbiota will become targets for therapeutic intervention.

Bultman, S. J. “Emerging Roles of the Microbiome in Cancer”. Carcinogenesis 35.2 (2013): 249-255.

RECENT SCIENCE ON CANCER AND THE MICROBIOME

Establishing the association of the oral microbiome with cancer risk may lead to significant advances in … opening a new research paradigm for cancer prevention.

Ahn, Jiyoung, Calvin Y. Chen, and Richard B. Hayes. “Oral Microbiome and Oral and Gastrointestinal Cancer Risk”. Cancer Causes & Control 23.3 (2012): 399-404.

Dietary or genetic obesity induces altera­ tions of gut microbiota, thereby increasing … various inflammatory and tumor-promoting factors in the liver.

Yoshimoto, Shin et al. “ObesityInduced Gut Microbial Metabolite Promotes Liver Cancer Through Senescence Secretome”. Nature 499.7456 (2013): 97-101. Web. 3 Oct. 2016.

Bacterial DNA load correlated inversely with advanced disease, a finding that could have broad implications in diagnosis and staging of breast cancer.

Xuan, Caiyun et al. “Microbial Dysbiosis Is Associated with Human Breast Cancer”. PLoS ONE 9.1 (2014): e83744.

High yogurt intake was significantly associated with decreased CRC risk, suggesting that yogurt should be part of a diet to prevent the disease.

Pala, Valeria et al. “Yogurt Consumption and Risk of Colorectal Cancer in the Italian European Prospective Investigation into Cancer and Nutrition Cohort”.

International Journal of Cancer 129.11 (2011): 2712-2719.

The gut microbiota also have important roles in limiting chemically-induced injury and proliferative responses that lead to tumor development.

Zhan, Y. et al. “Gut Microbiota Protects Against Gastrointestinal Tumorigenesis Caused by Epithelial Injury”. Cancer Research 73.24 (2013): 7199-7210.

Here, we identify the intestinal microbiota as a target of inflammation that affects the progression of colorectal cancer.

Arthur, J. C. et al. “Intestinal Inflammation Targets CancerInducing Activity of the Microbiota”. Science 338.6103 (2012): 120-123.

Optimal responses to cancer therapy require an intact commensal microbiota.

Iida, N. et al. “Commensal Bacteria Control Cancer Response to Therapy by Modulating the Tumor Microenvironment”. Science 342.6161 (2013): 967-970.

9 C3: WINTER 2016

A CONVERSATION WITH NOBEL LAUREATE, THOMAS R. CECH, PhD

BY GA RT H S U N D E M

C U BOULDE R

Distinguished Professor in the Department of Chemistry and Biochemistry, CU Boulder Director of CU BioFrontiers Institute

In 1982, a young CU chemist named Tom Cech was the first to show that RNA does more

bind to. Or you can actually see a drug candidate

than carry the information of DNA. RNA itself can initiate and regulate chemical reactions –

bound to the biomolecule and say, “Oh wow,

it is both genetic material and an effector of cellular processes. RNA might, in fact,

if we made this drug a little bigger on the left side,

spontaneously replicate itself, perhaps offering hints to the origin of life on Earth. For this

it would fit in this little pocket and it would bind

discovery, Cech earned the 1989 Nobel Prize in Chemistry. Since then, Cech, his lab, and

even better.”

the BioFrontiers Institute he directs have consistently pushed the field of biochemistry, constantly incorporating new technologies and new techniques. Here C3 talks with Cech,

C3: These things seem so close and yet

this perpetual futurist, about the direction of cancer research.

so far away…

Cech: We do what’s called fundamental science – to try to understand the basic biology behind some

C3: Where do you see the field of cancer

patients, it’s only 10 percent efficacious. But if you

of these questions of health and disease. We do

research heading?

could identify the responders ahead of time, and

this with the knowledge that there is usually a big

Cech: That’s an awfully broad question! I’ll pick

treat only that subgroup, the same drug would be

time gap between uncovering the basic knowledge

one area, but if you ask me again tomorrow, I might

highly effective. Now we’re starting to figure out

and actually making an impact on people. But

pick a different one. For the next 10–20 years, I

ahead of time who is most likely to be helped by

many of today’s breakthroughs – take immuno-

think precision medicine is a huge opportunity. In

any drug and we are enriching our clinical trials for

oncology – are based on basic science discoveries

spite of all the sequencing of human tumor samples

these people.

that happened 30 years ago. The work we’re doing

that is so popular right now, only in a small fraction

today will be of medical value in the future. It’s an

of cases does the genomic information give guid-

C3: And the other way precision medicine

ongoing process. If scientists were to stop discov-

ance on therapeutic direction. In the future, we’ll

will affect patients?

ering new aspects of human biology today, there

do a lot better. This whole field is in its infancy and

Cech: The other thing concerns treating the

would be no immediate difference at all, but 20

there’s a lot of hard work to be done to gain all of

patients themselves. In the future, if you have

or 30 years from now we would have lost out

the power from the human genome.

cancer or diabetes or heart disease or obesity or

on a big opportunity.

pulmonary disease, your doctor will be accompaC3: Is that because we still lack data or

nied by a new breed of genetic counselor. Instead

because we lack the ability to understand

of saying, “you’ve got obesity and should go on

the data we already have?

a diet,” they’ll say, “We’ve looked at your genome

Cech: Both. The two things go hand in hand – the

and your RNA and your proteins and your metabo-

ability to generate data and the ability to understand

lism and we don’t think most of these diets are

it. We’re still inventing technologies that will allow

going to do you any good, but we have some

us to collect better data. But the biggest challenge

more precise advice for you.”

THE PATH TO CLINICAL CARE

Basic Science

is in computational biology, to train a generation of biomedical scientists who can look at biology

C3: You seem to be constantly incorpo-

through the lens of this data.

rating new technologies in your lab, for

Drug Design

example taking advantage of the gene C3: How do you see this impacting patients,

editing strategy called CRISPR. What other

now or in the future?

new technologies do you think will speed

Cech: Two things. First is with clinical trials. I can

cancer research?

say this with great certainty because it’s already

Cech: One biggie is in imaging – to image indi-

happening. We know now that, for example, breast

vidual biological molecules with ever-increasing

cancer is not one disease but really perhaps ten

precision. For example, cryo-electron microscopy

major diseases and a bunch of minor ones that

is allowing pictures to be taken of complex biomol-

are only grossly lumped together with the term

ecules at the level where you can almost see the

“breast cancer.” For clinical trials, you might have

individual atoms. Both Anschutz and Boulder have

a drug that’s highly effective against one of the ten

recently upgraded our electron microscopes to

subtypes, so when you test it on all breast cancer

take advantage of this capability. You can see the surface of a biomolecule that a drug will need to

10 WWW.COLORADOCANCERCENTER.ORG

Pre-clinical Model

Human & Companion Animal Clinical Trials

FDA Approval

CLINICAL

CARE PAT RIC K C AMPBE LL

MD A Mix of East and West KAM DAR’S WO R LD J O U R N EY LAN D S I N C O LO RAD O

BY E R I K A MATI C H

Manali Kamdar’s journey to specializing in the treat-

“He basically helped her understand that she

ment of lymphomas with blood and marrow trans-

had put up a brave fight. He brought a deep sense

plantation took nearly a decade, with layovers in

of calm to her last moments. It was life-changing for

North Carolina, New York and Northern California.

me to see how the process of dying can be human-

But it all started in Mumbai, India with a little girl

ized so graciously,” says Kamdar. “I wanted to be

drawn to the arts and sciences.

like him and that day I decided to pursue oncology.”

“As far back as I can remember I was always

Next was a fellowship in hematology and

interested in liberal arts and in sciences,” says

oncology at East Carolina University. But another

Kamdar. “I was drawn towards the field of medicine,

decision was looming – what would Kamdar

research and its impact on human lives. With

choose as her sub-specialty? She was drawn to

respect to arts, the language of dance enamored

lung cancer and lymphoma. Some time as a guest

me. Juggling between school and dance recitals

fellow at Cornell University helped Kamdar make

was part of my life. They didn’t interfere – one ener-

up her mind. She chose to focus on lymphoma, a

Assistant Professor of Medicine,

gized me to learn the other and vice versa.”

cancer that begins in infection-fighting cells of the

University of Colorado School of Medicine

immune system. Kamdar then headed to Stanford

Clinical Director of Lymphoma Services,

Kamdar says it was obvious early on that she would be applying to medical school. She was

University for a third fellowship in blood and marrow

always curious to know the workings of the human

transplantation.

body. She wondered why things go wrong and once they’re fixed, can they break again?

Medical school is set up differently in India.

When Kamdar earned the chance to lead the lymphoma program for the University of Colorado, School of Medicine Division of Hematology, she

MANALI KAMDAR, MD

University of Colorado Hospital K.J. Somaiya Medical College, Mumbai India (MBBS) East Carolina University

It begins once a student finishes the United States’

was thrilled at the opportunity to build and create a

(residency, internal medicine)

equivalent of high school. It takes about four and a

robust lymphoma program that would offer cutting

East Carolina University

half years of rigorous training and because India is

edge medicine to patients.

(fellowship, hematology and oncology)

so populous, heavy emphasis is placed on clinical

“I love it here,” said Kamdar. “It’s not just the

skills. Then students take tests to see in which

natural beauty that the state is blessed with but

specialty they will continue their training.

people are very giving and accepting of each other.

“It so happened that I topped the state in pediatrics,” says Kamdar. “But as much as I Iove kids, that wasn’t my calling. That’s when it hit

Stanford University (fellowship, bone marrow transplantation)

I have spent time on each coast and this is the perfect mix of east and the west.”

Now that Kamdar has been in Colorado for

However there is always room for improvement,” said Kamdar. “The next six months here are actually

me how badly I wanted to practice adult medicine.

almost two years, some of her goals for the lym-

going to look very different since we will be offering

I turned down pediatrics residency and travelled

phoma clinical program are starting to be realized.

several new clinical trials to our patients.”

to the United States to pursue training in

Patient volumes increased substantially which led

internal medicine.”

to the successful recruitment of another lym-

particular her time in clinic where she gets to see

phoma specialist. Kamdar is also collaborating on

the true impact of lymphoma research on patients’

medicine resident at East Carolina University. That’s

several clinical and translational research projects

lives. “I love the clinical aspect of what I do because

when Kamdar believes fate stepped in.

with other investigators on the Anschutz Medical

I get to form meaningful relationships with my

Campus and looks forward to fruitful collaborations

patients,” she says.

She started her specialty training as an internal

“It was destiny how I got into oncology,” she says. “When I first started training in internal medicine, I thought I would subspecialize in

which will eventually improve patient outcomes.

“I hope to make our lymphoma program one of

She is enjoying every bit of this experience, in

In the midst of building the lymphoma program and taking care of patients, Kamdar tries to find time to enjoy her life outside of work.

cardiology. However, during one of the crossover

the top programs in the country. I realize there is a

rotations I witnessed one my mentors take care

lot of work that needs to be done but I have amaz-

of a cancer patient.”

ingly supportive colleagues and mentors and I am

burnt out, especially in the field of oncology,” she

positive we will achieve it,” she says.

says. “Spending time with my family and friends

Kamdar remembers it vividly. The woman was 75 years old and had been battling breast cancer

Kamdar’s research goal is ambitious. She wants

“I believe as physicians it is very easy to get

is by far my most favorite thing to do, followed by

for about 15 years and had progressed through

to be able to offer every lymphoma patient a clinical

dance, watching movies and trying new restaurants

many chemotherapy regimens and clinical trials.

trial within the next five years.

in the city. After all you live only once and it’s impor-

She says her mentor compassionately helped the woman come to terms with her illness.

“We all have to be aware that standard of

tant to give it your best and live life to the fullest.”

care treatment practices come from clinical trials.

11 C3: WINTER 2016

BY TAY L O R A B A R C A

N O P LAN S B UT

Life ITSE LF

J

AFTE R STAGE IV DIAGNOS I S, J E R RY WI LLIAM S CR E DITS PRAYE R AN D SCI E NCE FOR SUCCE SS

erry Williams has no big plans for his future. And he likes it that way. He’s already accomplished more than most people will in two lifetimes. Now, after 66 years, Jerry prefers to sit back, enjoy his family, and take time to read the newspaper.

Jerry, father of four, grandfather of 12, and great-grandfather of eight, served stateside in the United States Marine Corps and then enlisted in the Navy. In four years he traveled around the world three times on the aircraft carrier USS Ranger. During his time in the Navy, Jerry met his beautiful wife, Veronica, and they are celebrating forty years of marriage this year. After leaving the Navy, Jerry worked for the Department of Defense for nearly 31 years before retiring in 2010.

It was a few years into retirement when Jerry’s health suddenly started declining.

12

WWW.COLORADOCANCERCENTER.ORG

Jerry had been active all of his life. In high school he played basketball, football, and ran track and was accepted to the University of Colorado on a football scholarship. So, in May of 2015 when he could not shake a persistent, dry cough and lost nearly forty pounds in four months, Jerry knew something was not right.

“It would not go away, no matter what I did,” he says.

“The doctor prescribed me some cough syrup but it didn’t do anything so a few weeks later I went in for an x-ray.”

The x-ray showed something no one wants to see: three large tumors located in his left lung. A biopsy revealed that he had small cell lung cancer. Later, additional scans showed that the cancer had spread to the lining of his right lung, making it inoperable.

“It was a big shock. A life-changing shock. No one ever expects to hear they have stage four lung cancer,” Jerry says.

“But I did not have time to feel bad for myself. I had to get to work on beating it.”

Jerry and his primary care doctor started creating a treatment plan for him. Although he tried to remain positive, Jerry was very aware of his situation.

“I like to hear the bad news before the good and my doctor was very honest with me,” he says. “I was prepared for the worst, I gave my wife all of the passwords and showed her how to pay our bills online. I wanted to make sure she was ready. It was pretty traumatic.”

AN AG G R E S S IVE CAN C E R Small cell lung cancer (SCLC) makes up ten to 15 percent of all lung cancers. Even among other types of lung cancer, SCLC is infamous for its rapid growth and aggressive spread. At the time of diagnosis SCLC has often metastasized to other sites in the body and is typically treated with chemotherapy as the first line of defense. Standard treatments almost certainly will not cure stage IV SCLC and national survival rates are short.

“Unfortunately small cell lung cancer is a very aggressive form of lung cancer and the standard of care has not been changed for nearly thirty years,” explains Ross Camidge, MD, PhD, University of Colorado Cancer Center Investigator and director of thoracic oncology. “We are working to change that.”

Standard is not enough.

In June of 2015 Jerry started chemotherapy and initially responded well to it. His tumors shrank by nearly 75 percent.

However his cancer began to grow again in February of 2016.

“After chemotherapy stopped working my doctor recommended I consider going on a clinical trial,” explains Jerry.

“He used to work for the Cancer Center and was very familiar with all of the different studies here. He thought I would make a great candidate.”

Jerry made an appointment with Dr. Camidge to see if he was a good fit for a cutting-edge trial being offered at the University.

“I felt like participating in the trial was my best option because, quite frankly, I was out of options,” says Jerry.

“The chemo stopped working, the cancer had come back and there was nothing else anyone could do at that point. I never once hesitated or had a second thought about being a part of the study.”

With a fighter’s mentality Jerry started the clinical trial in April of 2016.

A G R O U N D - B R EAK I N G TR IAL Jerry was put on a combination of two new drugs, ipilumumab and nivolumab, in hopes that they would boost his immune system and help his body fight off the cancer.

Ipilumumab, commonly known as Yervoy, works to activate the immune system and help Cytotoxic T lymphocytes (T-cells) kill cancer cells. Think about it this way: the T-cells have the ability to destroy cancer cells but their growth is somehow blocked. Yervoy turns off the mechanism that damps down the T-cells and boosts their numbers. Yervoy is commonly used to treat melanoma but, on its own, has had little effect against lung cancers.

That’s where the second drug comes in. Nivolumab is a “checkpoint inhibitor”, also commonly used against melanoma, that works to block another strategy that cancer uses to escape T-cells. The combination of the two drugs seems to be the key for small cell lung cancer, not just boosting the numbers of T-cells but also making sure they are able to follow through and attack the lung cancer.

TAYLOR ABARCA

S O M E T H I N G I S N’T R I G H T

Jerry Williams is thankful to be a candidate for a cancer clinical trial

13 C3: WINTER 2016

During his first treatment on the drug combination therapy Jerry recalls looking at the patients around him and feeling incredibly blessed.

“I remember telling myself ‘you could have it so much worse, Jerry’,” he says. “’There are thousands of people going through this every day, be thankful that I am even a candidate for the trial’.”

Jerry did have some negative side-effects from the drugs but he never once thought about stopping the trial.

“After my first treatment I felt like I could not stand up, my eyes were extremely itchy, and my skin started flaking off,” he explains. “But by the second and third time they were gone and I felt pretty much back to normal.”

The response in the tumor on his scans has been dramatic.

At the appointment before the interview for this article, Jerry learned that his tumors had shrunken to nearly microscopic size.

“This treatment, which is looking to be one of the first real breakthroughs in this type of lung cancer for many decades, is now showing these sorts of responses in about 20 to 30 percent of people, with side effects, when they occur, mostly coming from the person’s own immune system attacking some of the good parts of their body as well,” says Camidge.

At the point of this interview, Jerry had been on the trial for exactly 25 weeks and he will continue to be on it as long as the combination controls his tumors.

“Unless the cancer progresses or the side effects start outweighing the benefits there is no reason for him to stop,” explains Camidge.

“Last year I felt like I was on death row,” says Jerry. “Now I am able to get up and run around with my great-grandkids.

People don’t believe me when I tell them I have cancer because I have put my weight back on. It is incredible.”

A M A N W ITH A B I G H EART Despite the fact that Jerry is going through treatment for stage IV small cell lung cancer, he is not as concerned with his wellbeing as he is with the well-being of the people around him.

“Going through cancer and cancer treatment is tough on me, but I feel like it is even harder on my friends and family,” he says. “I know that them having to watch me go through this is very upsetting, especially for the little ones.”

Luckily for Jerry he never once had to worry about a lack of support. As the third oldest of 12 siblings, he always had someone to take care of him, drive him to treatments, and go to all of his appointments.

“We are a family of preachers and nurses,” Jerry says.

“We believe in the power of prayer in combination with science.

I feel like I am living proof of that.”

14 WWW.COLORADOCANCERCENTER.ORG

“ We are a family of preachers and nurses.

We believe in the power of prayer in combination with science.

I feel like I am living proof of that. ” ~J E R RY WI LLI A M S

Although many people going through a cancer diagnosis often plan a “bucket list” of sorts, Jerry sees things differently.

He has no desire to travel the world, go skydiving, or climb a famous mountain.

“I have lived my life exactly how I wanted to,” he says.

“If I were to die tomorrow I would have no regrets. I am focusing on my time with the people I love.”

Jerry also sees the bigger picture when it comes to the importance of participating in a clinical trial. Unfortunately people of color are underrepresented in clinical trials, making it harder to discover which treatments work best in these populations.

Jerry wants to help change that.

“When I started the study I always said it would be great if it helped me but it would be better to help other people,” he says.

“If something they learned from me could help another person that is all I could ask for. The fact that I am still here today is just an added bonus.”

Do you have an inspirational story? Tell your story at http://story.coloradocancercenter.org or contact Garth.Sundem@ucdenver.edu.

ST RY INSIDE

T-ing Up to Destroy Cancer Cells Chances are you’ve heard of cancer immunotherapy, for example, the medicines that shrank Jerry Williams’s stage IV tumors. But while forms of immunotherapy can make a world of difference in some patients, it does nothing in others. Why is that? The answer has to

According to Cancer.Net, “Immuno­ therapy, also called biologic therapy, is a type of cancer treatment designed to boost the body’s natural defenses to fight the cancer. It uses substances either made by the body or in a laboratory to improve or restore immune system function.”

Let’s dive deeper. Imagine your immune system as a tiny army that fights off unwanted bugs in your body. Through complicated sensing mechanisms, it can tell the difference between “good guys” and “bad guys”. Although many different types of cells make up the immune system, it is the tiny hunters of T-cells that perform this essential function of scanning cells to make sure they are not a threat.

Unfortunately in some cases T-cells are deceived by cancer cells and, therefore, do not destroy them. Cancer researchers are working to learn more about the mechanisms that cancer cells use to trick T-cells into thinking they are “good guys” when in fact they are bad.

Enter immunotherapy.

The goal of immunotherapy is to stop cancer from growing or prevent cancer from spreading to other areas of the body, by helping the immune system recognize and destroy cancer cells.

Sound like a miracle? For some it is.

However immunotherapies do not work in everyone. One major reason, according to an article in the journal Science, is that it seems the immune system can only recognize cancer that has certain genetic mutations. Scientists can engineer an immune therapy to “seek and destroy” cancer that is marked by a particular mutation…but

T H INKST OC K

do with a cancer’s genetic makeup.

if your cancer does not have this specific mutation, immunotherapy may miss and the cancer may continue to evade your immune system’s T-cells.

The thing is, most cancers are born with numerous mutations and will develop even more mutations and other genetic changes as they grow. It’s like a tree: the root is formed by the original mutation(s), but above that, the tree is constantly growing the branches of new mutations. Not every cell will have every mutation. In fact, once you get out to the smaller twigs at the tips of the branches, few cancer cells may look alike. If an immunotherapy is built to target one of these “twig” mutations, it might not reach all – or even most! – cells.

It is not all bad news, though. For the patients whose cancer cells share a mutation targeted by immunotherapy, this new approach can be a literal life-saver. New science is leading to new treatments in this rapidly evolving field, and as more is discovered about how cancer works and what drives it, the more successful we are becoming at using tools you already have in your body to fight the disease.

Watch the video to learn more about CU Cancer Center clinical trials. Visit www.coloradocancercenter.org and click “Clinical Trials”

15 C3: WINTER 2016

STRONG is the New Healthy

I

n the second-floor weight room at the Anschutz Health and Wellness Center, 44-year-old Kristine Boyle is digging deep. Her face is flushed, biceps pumped, as she strains through the 10th repetition of a rowing exercise designed to strengthen her arms and back.

Nearby, her classmate Kim Peters, 55, is also working up a sweat, making her way through squats, hamstring curls and explosive “sand-ball slams” aimed at strengthening her abs and legs and jump-starting her metabolism.

At first glance, the 50-minute circuit workout looks a lot like what you’d find in a health club class. But these participants are unique. Along with her Spandex, Boyle wears a blue surgical mask to protect an immune system made fragile by a recent stem cell transplant for acute myeloid leukemia. Beneath Peters’ workout clothes is a chemotherapy port, in place to support the infusions she still gets every three weeks to battle ovarian cancer.

For them, this is more than a workout – it’s medicine.

“I couldn’t control that I got cancer, and I haven’t been able to control a lot of the things that have happened to me since.

But this I can control,” explains Peters, in between sets.

“This has been a gift.”

Boyle and Peters are among the more than 220 cancer patients to have benefited from the University of Colorado Cancer Center’s BFit BWell program, an individualized program that teaches cancer survivors how to exercise safely while studying the long-term benefits of fitness in cancer survivors. Now in its third year, the clinical/research program provides sharply discounted, one-on-one or group training for patients – many of them still in treatment – to help them gain stamina, boost lean muscle mass and, if necessary, lose fat. By doing so, research suggests they not only feel better short-term, they might also live longer.

“We know that patients who improve their fitness and body composition improve their ability to receive treatment, and in certain cancers – including colon cancer and breast cancer – can improve their chances of survival,” says Dr. Tom Purcell, associate director of clinical services for the cancer center, and the architect of BFit BWell. “We see it as an important component of an overall treatment plan.”

16 WWW.COLORADOCANCERCENTER.ORG

BY LI SA MA RS HA LL

CU RESEARCHERS EXPLORE HOW IMPROVING FITNESS AND BODY COMPOSITION CAN IMPACT LIFE FOR CANCER SURVIVORS

THE OBESITY-CANCER LINK Researchers have known for more than a decade that being heavy or sedentary can boost the risk of developing cancer in the first place. One 2010 report published in the journal Oncologist estimates that 20 percent of all cancers are attributed to being overweight or obese, with obesity the cause of 11 percent of colon cancer cases, 39 percent of kidney cancer cases, and 37 percent of esophageal cancer cases. Another recent study concluded that “just as smoking cessation leads to a reduction in lung cancer risk” when overweight, post-menopausal women slim down, they can reduce their risk of breast cancer by 50 percent.

The potential mechanisms behind the link are varied, explains Purcell: Excess fat tissue can boost the presence of hormones like estrogen, insulin, insulin-like growth factor 1, and adipokines which all play a role in the development, growth, or proliferation of cancer cells. Being overweight or sedentary can also boost inflammation, another key risk factor. But as Purcell, a clinical oncologist, points out, once a patient reaches his office, the more pressing question is this: Can starting an exercise and healthy eating program improve outcomes for patients who already have cancer? Absolutely, he says.

“Say I am diagnosed with Stage 3 colon cancer and I am labeled obese. If I can get my BMI down to less than 30, my overall chance of surviving colon cancer – chemotherapy aside – improves by 5 percent. That’s significant,” says Purcell.

Research on the impact that improved fitness and body composition can have on cancer survivors is mixed and relatively small, but growing. Some studies show that women who gain weight after a breast cancer diagnosis have worse survival rates; on the flip side, those who engage in regular physical activity are less likely to experience a recurrence. Obese colon cancer survivors have been shown to have shorter disease-free survival intervals and greater mortality rates. In contrast, among men who have prostate surgery to treat cancer, those who are lean and physically active afterward are less likely to suffer symptoms of incontinence than obese or inactive men.

Purcell stresses that his approach, and the BFit BWell Program, is more about building muscle and stamina and trimming fat than “losing weight.” In fact, he says, losing weight too fast post-treatment can be counterproductive.

PAT RIC K C AMPBE LL

Kristine Boyle (left) and Kim Peters work with trainers to support their cancer care

“Many of our patients don’t need to lose weight at all, but they do need to gain fitness,” he says. “We want them to be strong, not skinny. Strong is the new healthy.”

TAKING BACK CONTROL The BFit BWell program is open to patients diagnosed with cancer and currently undergoing treatment, with many finding their way to the program via referral or word of mouth within weeks of diagnosis. Each undergoes a personalized assessment at intake to determine what side effects from drugs or surgeries they may be experiencing, and how their trainer can customize a program to ameliorate or work around them. Patients pay roughly $20 per month to work out with a trainer one-on-one or in a semi-private group twice a week for three months.

If they are willing when they graduate, they undergo a detailed post-program assessment and their information is entered into a comprehensive data-base, enabling researchers to follow their health long-term.

Nicole Klocheck, the program manager, notes that often physicians don’t talk with their cancer patients at all about exercise, and when they do it’s with a vague recommendation to “stay active.” While general group yoga or exercise classes for cancer patients can be helpful, customization is optimal.

“What we are offering is a program tailored to the unique needs of the individual,” Klocheck says.

Ultimately, CU researchers would like to use the program as a platform for answering key questions: How can an individuallytailored exercise program impact things like recurrence and longterm survival rates? Do specific exercise protocols work better for certain cancer types than others? Do those with less common

cancers, like pancreatic cancer, also benefit from exercise?

And if so, when should they start? Two pilot studies are already underway, and several others are in the works.

“There is just not enough research yet for programs like this to be standard of care,” notes Ryan Marker, PhD, a postdoctoral fellow heading up the BFit BWell research effort. “We’re doing what we can to help push things in that direction.”

Already, research and patient testimonials are uncovering a wealth of short-term benefits, Marker says. Cancer and cancer treatments can lead to muscle wasting, fatigue, and loss of function, but exercise can help counteract all that. It can also help boost strength in areas weakened by surgery, like the abdominal area after treatment for ovarian cancer, or the shoulder after a mastectomy. And it can help fend off the weight gain that can sometimes result from fatigue and certain medications.

“We also know that exercise is safe for most cancer survivors, whether they have completed treatment or are still undergoing it,” Marker says.

Boyle joined the program September 8, less than three months after undergoing a stem cell transplant. She was weak from more than a month in the hospital, and her immune system was shot from two rounds of chemotherapy. But her trainers nudged her to do more than she thought she was capable of, and each week she got a little stronger.

Today she has more energy, better balance, sleeps better and has more mental clarity – all benefits she attributes to exercise.

But most importantly, she’s starting to feel like herself again.

“I remember laying in my hospital bed saying ‘I can’t wait to be able to work out again,’” recalls Boyle, an avid hiker and Crossfitter. “I’m not the person in that hospital bed anymore.”

17 C3: WINTER 2016

S U P P O R T E R

F CUS

S H E R MAN & HOWAR D, R EGI S B R EAST CANCE R FOU N DATION B R I NG WOM E N’S EVE NT TO M I LE H IGH STATION

BY LI N D SAY A N D R EWS Cancer assassins. That’s how Julie Clark, creator of

Under the care of Borges, Julie started an

Baby Einstein and speaker at this year’s Women’s

intense treatment plan that ended with a scan

Event, described the breast cancer team at the

marked “unremarkable.” The tumors that had

University of Colorado Cancer Center. On October

spread to her liver were gone.

6, Clark, along with more than 150 others, came

“Dr. Borges was so optimistic throughout the

together at Mile High Station to support female

entire process. She never once told me to ‘get my

cancer research.

affairs together’,” said Julie. “Because of her I cre-

The night started with Kim Christiansen, anchor from 9News, welcoming the guests. Virginia Borges, MD, director of the Young Women’s Breast

ated a new word, ‘oncotimistic’, the combination of oncologist and optimistic.”

The Women’s Event brought together physician

Julie Clark labels Dr. Borges as “oncotimistic.”

Because of the toll cancer has had on employ-

Cancer Translational Program and the Robert F.

scientists, patients, and philanthropists to move the

and Patricia Young Connor Endowed Chair in

needle in cancer care, and was made possible by

ees, Sherman & Howard feels very strongly about

Young Women’s Breast Cancer Research, then

incredible sponsors including Sherman & Howard,

sponsoring the event.

took the stage to explain the importance of the

L.L.C. and the Regis Breast Cancer Foundation.

event and the critical impact it has on research.

“The Sherman & Howard Women’s Initiative

“Like any large employer, cancer frequently has hit Sherman & Howard’s employees and their

Next, Julie Clark shared her emotional and inspiring

is proud to be the supporting sponsor of the

families, and we are intimately familiar with the diffi-

story about her own battle with breast cancer.

Women’s Event. One of our members, Kathy Odle

culties that come with a cancer diagnosis,” Murphy

Kortz, first presented the sponsorship idea to us

says. “Several members of our Women’s Initiative

the young age of 37 she beat her initial diagnosis,

several years ago and the firm has been a repeating

and their families have battled cancer in the past

but her cancer returned with a vengeance just four

sponsor of the Women’s Event since then,” says

few years. We are proud to have a world-class

years later. This time, her diagnosis was worse.

Hilary Murphy, from Sherman & Howard. “The firm’s

cancer center right in our backyard and we support

Her cancer had spread to her liver and she was

Women’s Initiative was excited to support a cause

the CU Cancer Center’s cutting edge research and

told to ‘get her affairs together’.

that has affected each of us in some way, whether

excellent care providers, so that the entire Sherman

Julie is a two-time breast cancer survivor. At

having loved ones who have battled cancer or

& Howard family can look forward to a day when

daughters would have to grow up without their

having been diagnosed ourselves. Cancer diagno-

cancer is no more.”

mommy,” Julie said. “I think this is what makes

sis and treatment are so critical and we are proud

breast cancer so hard. It takes mommies away

to support the CU Cancer Center and its mission to

from their children. It takes sisters, daughters

make inroads against the disease through research,

and wives.”

clinical trials, prevention and cancer control.”

LYN N CLARK

“My ultimate fear was that my two young

The Regis Breast Cancer Foundation also contributed as a title sponsor to the Women’s Event.

“We are thrilled to sponsor the event because we know the funds we raise will help move the needle on research and treatment programs for women’s cancers at the University of Colorado Cancer Center,” says Brenda Hayes from the Regis Breast Cancer Foundation.

Through the event, more than $30,000 dollars was raised to support female cancer research.

Grants from the National Institutes of Health or other major governmental sources are typically used to move forward projects that have already demonstrated significant promise. But how do researchers demonstrate this promise in the first place? Increasingly, grants like these from the Women’s Event and philanthropic support are used to fund the most innovative, new ideas that could lead to tomorrow’s treatments against cancer.

“I am overjoyed,” said Borges. “The funds raised

Virginia Borges (left), MD and Jennifer Richer (right), PhD, at the Women’s Event

from events like this are helping us beat these horrible diseases. I, along with all of the doctors working on female cancers, could not be more appreciative.”

18 WWW.COLORADOCANCERCENTER.ORG

LY NN C LARK

Women’s Event Supports Research

C O M M U N I T Y

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$300,000 AWARDED TO UNIVERSITY OF COLORADO CANCER CENTER FOR PROMISING CHILDHOOD CANCER RESEARCH Three University of Colorado Cancer Center investigators are among those receiving grants for their work from the St. Baldrick’s Foundation, a volunteer-powered charity dedicated to raising money for the most

EVENTS

promising childhood cancer research. Every two minutes a child is diagnosed with cancer worldwide.

The Men’s Event, an institution in the phil-

One in five kids diagnosed in the U.S. will not survive, and of those who survive, two-thirds will suffer from

anthropic community, has increased prostate

long-term effects from the very treatment that saved their life. As the largest private funder of childhood

cancer awareness, as well as supported

cancer research grants, St. Baldrick’s supports the best research no matter where it takes place, giving

research to increase quality of life and survival

hope to every child.

rates. Each November, hundreds of supporters

James DeGregori, PhD, CU Cancer Center’s associate director for basic research, received $100,000

attend this event to make a significant impact

to investigate improving therapies for acute myeloid leukemia (AML) which represents 20% of child-

on the CU Cancer Center’s work. Since 2007,

hood leukemias.

this event has raised nearly $900,000 dollars in

CU Cancer Center member and St. Baldrick’s Scholar Jean Mulcahy Levy, MD, also continues to

valuable private support for cancer research.

receive support for her work in pediatric brain tumors with a $115,000 grant.

The Women’s Event supports the University

“Having the support and the endorsement of my project from a nationally recognized organization has

of Colorado Cancer Center and female research-

helped me obtain additional support from other, smaller organizations for lab supplies to buy specialty

ers focused on women’s cancers. “Fund the

items needed for my project that are not typically stocked in my mentor’s lab. This made me competitive

Mission” – a paddle raiser emceed by 9NEWS

for national funding and has enabled me to obtained highly competitive NIH funding which is essential as

anchor Kim Christiansen – gives attendees the

I am transitioning into my first faculty position,” says Mulcahy Levy.

opportunity to make gifts in support of research.

Based on progress to date, CU Cancer Center’s Adam Green, MD, was awarded a new $97,500 grant LYNN CLARK

to fund an additional year of his St. Baldrick’s Fellow award. High-grade gliomas (HGG) are brain tumors that are usually fatal in children. Green’s work has recently shown promising results using a new medicine called Selinexor in laboratory models of HGG. Green believes Selinexor works by restoring the function of

PATRICK CAMPBELL

proteins that suppress the tumor and acts as the brakes in cancer cells.

Dinner in White is a unique, annual “pop-up party” held every August on a Saturday evening.

Inspired by Diner en Blanc in Paris, this popular fundraising event is like no other. The location is kept secret until one hour before the party begins, when guests (clad in all white attire) are welcomed with entertainment, music and fun.

Part of the event is dedicated to a survivor story, highlighting advances in treatment at the CU Cancer Center.

Undy 500, a family-friendly 5K raises funds and awareness for colorectal cancer research, while also celebrating survivors and honoring loved ones lost to colon cancer.

CANCER LEAGUE OF COLORADO CELEBRATES MOST SUCCESSFUL FUNDRAISING YEAR IN ITS HISTORY The Cancer League of Colorado presented Dan Theodorescu, MD, PhD, University of Colorado Cancer Center director, with a check for $690,000, the highlight of over $1m in donations during the record fundraising year for the all-volunteer nonprofit organization.

This substantial amount is in addition to $30,000 donated for cancer research at National Jewish

Golfers Against Cancer (GAC) is a national

Health; $178,500 that has been granted to 31 different organizations in Colorado that support cancer

organization founded in 1997 by a group of

patients and their families; and $150,000 that has been committed to CU Cancer Center for investigator-

golfers who had lost two of their golfing buddies

initiated clinical trials to be launched in 2016.

to cancer. Motivated to raise money to fund

Founded in 1969, Cancer League of Colorado is the fundraising leader for cancer research in the state

cancer research, they created this annual golf

of Colorado. Its partnership with the CU Cancer Center also includes the Cancer League of Colorado

tournament and auction.

Endowed Chair, established in 2015 and awarded to the director of pediatric neuro-oncology at Children’s Hospital Colorado, Rajeev Vibhakar, MD, PhD, MPH as a source of perpetual funding for a leading cancer scientist. Cancer League of Colorado has always been run entirely by volunteers, with membership dues offsetting costs of any minor expenses of running the organization.

Visit www.cancerleague.org for more information or to make a donation.

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WI NTER 2016

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R ET U R N S E RV I C E R E Q U E ST E D

C3: Collaborating to Conquer Cancer Published twice a year by University of Colorado Denver for friends, members and the community of the University of Colorado Cancer Center.

(No research money has been used for this publication.)

Editor: Garth Sundem | 303-724-6441 | garth.sundem@ucdenver.edu Contributing Writers: Taylor Abarca, Lisa Marshall, Erika Matich Photos: Patrick Campbell The CU Cancer Center Consortium Members UNIVERSITIES

Colorado State University University of Colorado Boulder University of Colorado Denver INSTI TUTIONS

University of Colorado Hospital Children’s Hospital Colorado Denver Veterans Affairs Medical Center Visit us on the web: www.coloradocancercenter.org The CU Cancer Center is dedicated to equal opportunity and access in all aspects of employment and patient care.

T H E

M E S S A G E

Accelerating the Pace of Cancer Research

A

s you may have heard, we are in the middle of a “Cancer

3. PRIVATE PHILANTHROPY

Moonshot” meant to make 10 years of progress against

In this day and age, both young and established investigators

the disease in only 5 years. Looking at this another

struggle to compete for funding from the National Institutes of

way, the goal of the Moonshot is to double the pace of cancer

Health and other major sources. Thus many “out-of-the-box”

research. Now, as never before, this ambitious goal is possible.

innovative ideas that may fail ... but may also lead to revolutionary

The following three pillars will help us accelerate to twice our

new inroads against cancer, are not tried. Funding of these ideas

current speed in our progress against the disease:

depends on pilot grants and, increasingly, these pilot grants come from private philanthropy. This also means that philanthropy has

1. COLLABORATION

more power than ever before to contribute to the pace

Cancer is a disease driven by the very fundamentals of

of research.

science – molecular biology, genetics, pharmacology, physics, chemistry, and many more. Because cancer science is now so specialized, no single person has all the expertise required to

FROM THE DIRECTOR DAN THEODORESCU, MD, PhD

deepen our understanding of the disease and we depend on our collaborators more than ever. Progress against the disease will accelerate as teams of scientists from diverse disciplines learn to work together, contributing their unique expertise to a

“With your help, we are helping launch the careers of the next generation of cancer scientists and push forward with some of the most creative ideas in the field.”

shared goal.

At the CU Cancer Center, we are uniquely positioned to 2. DATA SHARING

drive this era of acceleration. As a “comprehensive” cancer

What genetic features may allow us to target a tumor?

center, we have teams representing each step on the path from

Which medicines or treatments work best against which kinds

the laboratory to the clinic. As part of the Oncology Research

of cancer? How can cancer survivors live the best possible lives,

Information Exchange Network (ORIEN) we give our data power

and are there approaches that can prevent cancer in the first

by combining it with that of 12 other leading institutions. And

place? It may be that no single cancer center could ever see

with your help, we are helping launch the careers of the next

enough patients to truly answer these questions. Instead, the

generation of cancer scientists and push forward with some of

pace of our progress against cancer is accelerating as more

the most creative ideas in the field. The promise and real potential

centers share more data.

of the Moonshot makes this a more exciting time than ever before in cancer research and treatment. With your help, the CU Cancer Center can accelerate the goal of a cancer-free world.

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