C3: Collaborating to Conquer Cancer Fall 2017 Edition

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 2017

Serendipity IN SC IENCE

12: WHEN THE STARS ALIGN

10: Q&A WITH KIAN BEHBAKHT, MD 11: C3 MD GRETCHEN AHRENDT, MD 16: ECLIPSING THE SUN

ANSCHUTZ MEDICAL CAMPUS

N3WS C U C ANC E R C E NT E R

FAT RATS SHOW WHY BREAST CANCER MAY BE MORE AGGRESSIVE IN PATIENTS WITH OBESITY A CU Cancer Center study offers a possible explanation for the fact that women with obesity are more likely to get breast cancer: In an animal model of obesity and breast cancer (affectionately referred to as the “fat rat”), tumor

C H R I STO P H E R L I E U , M D , TO L E A D C O M M I T T E E F O R I N V E S T I G AT O R - I N I T I AT E D TRIALS

cells in obese animals but not lean animals had especially sensitive androgen

W ELLBERG

receptors, allowing these cells to magnify growth signals from the hormone

Many clinical trials are managed

testosterone. Similar to the way in which many breast cancers drive their growth

by drug companies hoping to test

with estrogen receptors, these tumors in obese rats drove their growth with

the promise of new medicines.

androgen receptors.

Investigator-initiated trials allow

“Our original goal was to make a model of obesity and breast cancer in which

doctors and researchers to test

we could test anti-estrogen treatments. At first, we were disappointed to discover that rats don’t make much

treatments that their own hands-

estrogen in fat tissue like humans do. But we then realized that this aspect of the model gave us an excellent

on experience in the lab and clinic

opportunity to study cancer progression after anti-estrogen treatment. Because fat cells in these rats don’t

imply may offer meaningful results.

make estrogen, they are like human breast cancer patients treated to remove estrogen. This allowed us to

Christopher Lieu, MD, CU Cancer

ask what is responsible for obesity-associated tumor progression in conditions of low estrogen availability,”

Center’s deputy associate director

says Elizabeth Wellberg, PhD, the paper’s first author.

for clinical research, has received a 2017 National

About 40 percent of American women have obesity; about 75 percent of breast cancers are estrogen-

LI EU

Cancer Institute Cancer Clinical Investigator Team

receptor positive, most of which will go on to be treated with anti-estrogen therapies. This combination

Leadership Award (CCITLA), which he will use

means that thousands of women every year could benefit from treatments aimed at the aspects of obesity

to further develop the capacity for CU Cancer

that promote breast cancer in low- or non-estrogen environments.

Center to host investigator-initiated clinical trials.

“This award provides support to ensure we are

ROHIT TANDON

doing things the right way, improving education NEW CLINICAL TRIAL FRAMEWORK

particularly for clinical investigators and standard-

TESTS ‘NATURAL’ CURES FOR CANCER

izing the way we conduct investigator-initiated

A CU Cancer Center clinical trial is now recruiting

research,” Lieu says.

prostate cancer patients, who would otherwise be

“Chris’s own innovative trials are providing

on a watch-and-wait protocol, to test the ability

new options for colorectal cancer patients,

of grape seed extract to slow the rise of prostate-

especially patients who happen to be young,”

specific antigen (PSA), a common marker of

says Dan Theodorescu, MD, PhD, director of

prostate cancer progression. The trial is the

the CU Cancer Center. “This honor from the NCI

result of a series of CU Cancer Center studies

will help Chris guide other CU Cancer Center

demonstrating the promise of grape seed extract in

investigators in their ability to design, manage

preclinical models of prostate cancer, in collabora-

and recruit patients for their own innovative,

tion with doctors at University of Colorado Hospital who treat the condition. In addition to testing grape

investigator-initiated clinical trials.”

seed extract, the trial provides the framework to test other promising compounds in this setting, potentially including additional compounds derived from natural sources.

“In this window, we would only be watching these patients – our trial is an alternative to observation, not an alternative to treatment – and we’ve shown that grape seed extract is unlikely to cause side effects.

So why not take this opportunity to test some of these promising compounds, starting with grape seed extract?” says Paul Maroni, MD, investigator at the CU Cancer Center and associate professor of Surgery at the CU School of Medicine.

The trial will enroll 40 men with asymptomatic, non-metastatic prostate cancer with rising PSA, who will take 150 mg of grape seed extract by mouth twice daily. These men will then be evaluated every 6 weeks for a year to measure the progress of their cancer.

“Ultimately, if grape seed doesn’t change how we approach these patients, then we’ve built a program to examine other complementary or low-side-effect medicines. If grape seed extract doesn’t work, we can take this protocol, put in a new background – bitter melon, milk thistle, etc. – and examine that,” Maroni says. Many drugs currently used against cancer originated from substances found naturally. Now this approach that uses the tools of Western medicine to evaluate what some would consider Eastern ideas may allow doctors to add to this list of naturally-derived compounds that aid our fight against cancer.

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E F F E CTIVE TE STI N G

REFUTING THE IDEA THAT MUTATIONS CAUSE CANCER

C ASE Y C ASS

MORE

Most of us believe that the longer we live, the more chance that awful luck will result in a random, cancer-causing mutation. But James DeGregori, PhD, deputy director of CU Cancer Center offers evidence that cancer is caused by more than just mutation. He points to forces of natural selection acting within the microenvironment – the ecosystem of the body’s tissues. In his evolutionary theory of cancer, DeGregori points out that cells containing dangerous

NEW APPROACH TO GENETIC TESTING

mutations exist all the time, but are commonly out-competed by healthy cells

MATCHES LUNG CANCER PATIENT

that are optimized to live in healthy tissue. It is only when the tissue micro­

WITH LIFE-SAVING DRUG Testing individually for each possible cancercausing genetic alteration would require

DEGREGORI

environment is degraded (by smoking, sun, chemical exposure, age, etc.) that cells with these mutations suddenly find themselves most fit and are able to

hundreds of individual tests and many, many

out-compete healthy cells and so establish themselves in the landscape of the body. Mutations are still

thousands of dollars. A CU Cancer Center case

required for cancers, but it is changes in our tissues as we age or engage in activities like smoking that are

study highlights an alternative: Use testing that

the primary determinants of “who gets cancer, how cancer risk relates to known causes, which tissues it

can look for gene alterations in many genes

occurs in, and when the cancers develop in life,” DeGregori writes.

simultaneously. The technique results in the first

One implication of this line of thought is that research into cancer prevention has been approaching the

published report describing successful target-

disease from the wrong angle. If the field believes that mutations are the major factor causing cancer, then

ing of MET fusion in a lung cancer patient.

preventing cancer depends on preventing mutations. However, if the field looks through DeGregori’s lens of

In this study, researchers examined the

evolutionary competition between cancer cells and healthy cells, dependent on their relative adaptation

tumor sample from a late-stage lung cancer

to microenvironments, then preventing cancer depends on maintaining a tissue ecosystem that favors

patient using an assay that detects gene

healthy cells.

fusions in dozens of genes. The test identified a rare fusion involving the gene MET,

“We are not going to anytime soon come up with technologies to prevent most mutations. But manipulating the microenvironment? That’s more approachable,” DeGregori says.

leading researchers to treat the cancer with the targeted therapy crizotinib, which inhibits MET signaling (among other kinds of signal-

CU CANCER CENTER CONSULTS ON KING COBRA CONUNDRUM

ing). Now more than 8 months after the start

A keeper at the Denver Zoo, Tim Trout, noticed that a king cobra had lost some weight and had lesions on

of the targeted treatment, the patient who was

his skin. A biopsy, blood work and x-rays, all taken during a stressful medical procedure with the 12½-foot

diagnosed with stage IV lung cancer continues

venomous snake, revealed it had cutaneous lymphoma, a rare cancer that affects the skin.

to show an almost complete response.

So now what? That’s where CU Cancer Center member Douglas Thamm, VMD, DACVIM, enters the story. He is the Barbara Cox Anthony Professor of Oncology at the Flint Animal Cancer Center at Colorado State University. CSU is part of the CU Cancer Center consortium of research institutions.

“This was obviously an unusual situation,” says Thamm. “This animal is very, very, very hard to handle.

STUDY FINDS BREAST CANCER DRIVER, HER2, IN 3 PERCENT OF LUNG CANCERS

The only way to administer chemotherapy drugs would be to knock him out completely.”

The good news for the snake is that a medication called lomustine (CCNU), used in dogs and cats with

The Lung Cancer Mutation Consortium at CU

cutaneous lymphoma, comes in tablet form. The pill lasts approximately three weeks. The cobra just so

Cancer Center reports in the journal Cancer that

happens to eat about every two or three weeks so the pill could go in the cobra’s food.

24 of 920 patients (3 percent) with advanced-stage

“This was a bit like the Wild West – let’s try what we know from treating other critters, because we know what happens if we don’t try anything,” Thamm says. “It may be too early to talk about the outcome,

The gene HER2 has been known as a breast

but he seems to be doing well and this treatment didn’t hurt him.”

cancer driver, with therapies approved to target HER2 mutations in this setting. Now ongoing clinical trials are evaluating the use of HER2-directed

R USHEN B

lung cancer had mutations in the gene HER2.

therapy against lung cancer testing positive for the mutation. By identifying a significant population of HER2+ lung cancer patients, the current study demonstrates the need for these therapies.

Early data offers hope. Of the 24 patients identified with HER2 mutation, 12 received HER2-directed therapy and 12 received conventional therapies (e.g. chemotherapy). Median survival for patients receiving HER2-directed therapy was 2.1 years compared with median survival of 1.4 years for those who did not receive HER2-directed therapy.

3 C3: WINTER 2017

PH OT O-ILLUST RAT ION BY H E LE N Y OUNG

Serendipity IN SCIENCE

HOW LUCK – AND THE COURAGE TO LOOK WHERE IT LEADS – DRIVES T H E D I R E C T I O N O F S C I E N C E A N D S C I E N T I ST S AT C U A N D B E Y O N D

S

ay what you want about Dennis Rodman, but you can’t deny the dude knew how to grab a basketball. Like game six of the 1996 NBA finals against the Seattle Supersonics, when Ron Harper put up a fourth-quarter 3-pointer

that bounced off the backboard right into Rodman’s hands for an easy put-back – he was just lucky to be in the right place at the right time. A 2011 interview in the Detroit Free Press with his Pistons teammate, Isiah Thomas, sheds a little light on this luck.

BY GA RT H S U N D E M

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When an unexpected result shows up in the petri dish, it takes confidence to see it as a discovery instead of a mistake.

PETER WILLIAMS

PE T E R WILLIAMS

“We were standing in the lay-up line, warming up and shooting,” Thomas says, “and Rodman was standing back and watching everybody shoot. I said, ‘Hey, come on, you have to participate; everybody’s shooting lay-ups, you have to shoot lay-ups, too.’ And he said, ‘I’m just watching the rotations on the basketball.’ That’s how far Rodman had taken rebounding. He knew the rotation of every person that shot on our team. He had rebounding down to a science, and I never heard anyone think or talk about rebounding and defense the way he could break it down.”

The point is that what looked like luck was actually science. On the other hand, what looks like science is sometimes luck. There’s the famous story of Raytheon engineer, Percy Spencer, experimenting with radar equipment in 1945 when he realized the chocolate bar in his pocket was melting – leading to the invention of the microwave.

Or the story of Charles Goodyear spilling rubber, sulfur and lead to invent vulcanized rubber. But the thing about luck is Spencer had to realize that something more than his body heat had melted the chocolate bar. And Goodyear had to poke and prod the mess on his stove before just throwing it all out.

Cancer science is the same way. Often scientists create their own luck. When a lucky door opens, it takes courage to step through. And when an unexpected result shows up in the petri dish, it takes confidence to see it as a discovery instead of a mistake. Call it luck, call it science…we call it serendipity. Here are just a handful of the serendipitous experiences, straight from our researchers’ mouths, that have helped to push cancer discovery forward at CU.

ANDREW THORBURN, PhD Professor and Chairman, Department of Pharmacology, CU School of Medicine In the mid 1990’s, my lab was starting to look into how normal cells and cancer cells die. In an early experiment, my wife, Jackie, who is also my lab manager, separated a prostate cancer sample into tumor cells and healthy cells, which we hoped would let us search for something that would kill tumor cells but not the normal cells. Part of the experiment required adjusting a certain protein in the cancer cells so they wouldn’t commit a kind of cellular suicide before we could do our “real” experiments. By that point, hundreds of scientists had used this same technique on cancer cells, tweaking this protein to keep them alive, but because we hoped to compare the results of subsequent experiments to our controls, we had to treat the healthy cells in the same way.

What happened was odd: This protein worked exactly as we expected in cancer cells, stopping them from dying. But it did the exact opposite in healthy cells – it killed them.

Now, this was just the control experiment and we didn’t actually want to kill normal cells anyway, so most people might have just ignored this weird result and concluded that they had mixed up the samples or something like that. But Jackie was smart enough to look into it further. Over the next few years we discovered that this protein had a very unique ability to kill only normal cells, not tumor cells and when it did so, it seemed to be associated with the activation of a process called “autophagy,” which is a bit like a cellular recycling program.

It changed the entire direction of my lab’s research, encouraging us to focus on autophagy. Now my former postdoc, Jean Mulcahy-Levy, MD, a pediatric oncologist over at Children’s Hospital Colorado, is deliberately manipulating autophagy in patients to improve therapy, with promising results. It all came from Jackie getting the opposite result from what you’d want—killing normal cells but not cancer cells with the thing that was supposed to actually block cell death.

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ANDI DWYER Co-Director of the Colorado Colorectal Screening Program at the University of Colorado Cancer Center and Program Director at the Colorado School of Public Health Almost a decade ago, not long after I started working with the Colorado Colorectal Screening Program, I spoke at a 9Health event about the importance of screening and early detection in colorectal cancer. After the event, I was impressed but slightly jealous of all the attention that breast cancer received and I decided we had to do something proactive to raise awareness. When I chatted about my goal with a colleague at the American Cancer Society, he told me that he was in a band with one of the producers of the TV show South Park. After speaking with the producer, he agreed to help us create a video, which we ended up titling “Jo Jo: Your Colon and You.” The irreverent video was picked up by NPR, played in movie theaters and shown in clinic waiting rooms across the country. Jo Jo also won the 2013 Scientific Health Messaging Award of the year for the American Public Health Association. Indeed this weird connection certainly helped us get the word out about CRC screening!

PETER WILLIAMS

CATHY BRADLEY, PhD Associate Director for Population Sciences Research, CU Cancer Center David F. and Margaret Turley Grohne Endowed Chair for Cancer Prevention and Control Research at the Colorado School of Public Health When I was first studying employment outcomes of cancer survivors, our computer system crashed and we lost a whole bunch of data. To guard against that ever happening again, I decided we would start recording our interviews – then if there was another computer crash, at least we could go back and listen to the taped interviews to recreate our data. Interestingly, at the time we had been finding only a very modest effect of cancer on employment – most people who got cancer stayed employed and this made it seem like cancer may not have a dramatic effect on patients’ lives beyond their disease.

One day I happened to be listening to the tape of an interview with a woman with breast cancer who was a school bus driver. She talked about how she got up early, took kids to school, went to get her chemo, and then went back to pick up kids at school to take them home. And she said something very important – she said that if she couldn’t keep that schedule, she would miss her chemotherapy before she missed work. Our interviewer asked a little more and found out that for this woman losing her job would mean losing health insurance. It turned out that the reason that cancer had such a small effect on employment is that due to concerns about health insurance, cancer patients often just had to keep working anyway. Now, I can’t tell you how many times we recorded interviews and ended up with information we didn’t expect. And the whole reason we started recording in the first place was due to a computer crash.

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PE T E R WILLIAMS

“It turned out that the reason that cancer had such a small effect on employment is that due to concerns about health insurance, cancer patients often just had to keep working anyway.” ~CATHY BRADLEY, PhD

PE T E R W ILLIAMS

STEPHEN WITHROW, DVM Founding Director of the CSU Flint Animal Cancer Center Distinguished Professor, Colorado State University

PETER WILLIAMS

In the early 2000s, veterinary oncologists up here at the CSU Flint Animal Cancer Center started noticing something strange in our bone cancer patients – they got surgery, they got chemotherapy, and then about 40 percent of dogs with bone cancer went on to develop a bone infection called osteomyelitis. Now, infections are one of the most dangerous post-surgical complications, leading to deaths in both canine and human patients. But we saw that the dogs with this infection actually lived longer on average than dogs with no infection, actually on average about twice as long. When we looked into why, we found that elements of the immune system that were activated against the infection also helped to keep cancer in check. In 2010, we published the study in a journal for advances in human cancers and I presented our findings at a meeting for surgeons and oncologists. No U.S. researchers ran with our finding, but I got a call a few months later from an MD in England named Lee Jeys who had done a similar study looking into infection and survival rates in kids with bone cancer, and found that 10-year survival rates for infected kids was 84.5 percent compared with 62.3 percent of uninfected patients. How to implement this in a clinical setting is still an open question, but now researchers at CSU like Steven Dow, DVM, are looking into how we can use infection – which is usually a bad thing – along with other therapies to help fight bone cancer.

CHRIS LIEU, MD Director of the CU Cancer Center Colorectal Oncology Program When I was an intern at the VA, Steve Leong was a fellow at the same hospital and because we looked alike, we were always being mistaken for each other – people would be asking me for chemotherapy orders, which was way beyond my experience at the time, and asking him to handle a patient’s potassium replacement, which is an intern’s job! Through this ongoing case of mistaken identity, we got to know each other pretty well and talking with Steve helped spark my interest in hematology and oncology.

When I was looking for a research mentor, Steve introduced me to his mentor, Dr. Gail Eckhardt, MD, here at CU who became my scientific mentor and helped propel me into a fellowship at MD Anderson. And that was my start! I like to think that Steve and I would have become friends even without people thinking that we were one person, but I’m really not sure where my career would have led without this lucky mix-up.

“Researchers at CSU are looking into how we can use infection – which is usually a bad thing – along with other therapies to help fight bone cancer.” ~STEPHEN WITHROW, DVM

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PE T E R W ILLIAMS

DANIEL POLLYEA, MD Clinical Director of Leukemia Services at CU School of Medicine When I was a first-year fellow in hematology/oncology at Stanford, fellows had to present journal articles at a weekly meeting, where faculty enjoyed grilling the presenter to ensure he/she understood the paper. When it was my turn, the paper I chose happened to be from the lab of Craig Jordan, chief of the Division of Hematology here at CU, describing a new therapy he was developing to target leukemia stem cells. I was intrigued by his idea that a small population of stem cells was the root cause of leukemia, in this case acute myeloid leukemia (AML), and that these stem cells, which could almost never be eradicated by conventional therapy, were a common source of relapse.

Over the course of my preparation I learned that paper very well, and starting then, became fascinated with the biology of leukemia stem cells and the potential to target them in the clinic.

Years later, I came to CU as junior faculty in Hematology and Craig was recruited from the University of Rochester a few years after that to be the division chief. We immediately began to collaborate, and decided that the central theme of our Division would be the study of leukemia stem cells and the clinical development of targeted therapies to eradicate this population. Now, this interest that started when I happened to pick up one of Craig’s journal articles long ago has turned into a collaboration in which I get to help Craig test the drug venetoclax, which you can read about elsewhere in this magazine.

STEPHEN LEONG, MD Associate Professor, Division of Medical Oncology, CU School of Medicine A handful of years ago, I was the principal investigator on a phase I clinical trial of a new drug being tested to treat a range of advanced solid tumor types. One of the patients on the trial happened to have adrenal cancer, a rare, aggressive cancer that is most commonly diagnosed in patients in their 40s and 50s. Though the drug didn’t go on to earn FDA approval, this patient had a reasonably strong response and he posted about his experience in a support forum for people with adrenal cancer. Suddenly we started getting calls from all over the country from patients who wanted to explore having their adrenal cancer treated here at CU. Now, very few centers are able to do research in adrenal cancer – there just aren’t enough patients at any one center to draw meaningful conclusions. But there we were because of this forum post all of a sudden seeing three, four, even five adrenal cancer patients every week. With patients’ permission, we started banking tumor samples to use for experiments and our team here has become a real leader in the field of adrenal cancer research.

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P ETER W ILLIAM S

“This interest that started when I happened to pick up one of Craig’s journal articles long ago has turned into a collaboration in which I get to help Craig test the drug venetoclax.” ~DANIEL POLLYEA, MD

“We think that Semaphorin 7A – this protein whose effect we stumbled onto purely by chance – might actually be a marker for patients that will benefit from immunotherapy.” ~TRACI LYONS, PhD PE T E R WILLIAMS

TRACI LYONS, PhD Assistant Professor, Division of Medical Oncology, CU School of Medicine In 2014, I had just learned I was getting my own lab and decided that I would focus part of my research on how cancer cells migrate through lymphatic vessels. To get up to speed, I decided to attend a research conference in Italy on lymphatics and happened to notice on the list of attendees the name Beth Tamburini. She and I had been in grad school together here at CU and I noticed that, like me, she was also still here. Out of the blue, I emailed her and said, “I’ll see you in Italy!” and we ended up spending the conference catching up.

It turned out that Beth is in immunology, studying how lymph vessels work with the immune system. And I was studying how lymph vessels provide avenues for cancer metastasis. We kept in touch but we were both busy and it was another two years before we got back in touch…at another conference! This time when we talked, we decided on an experiment we wanted to do together.

Basically, for various reasons, we wanted to see if a protein called Semaphorin 7A would make mouse models of cancer grow more lymph vessels. The idea was we would give some mice regular cancer cells and others cancer cells overexpressing Semaphorin 7A and then compare the growth of lymph vessels. But we accidentally put some cancer cells into mice with an antigen that activated the immune system – when these immune systems rejected cancer cells before tumors could grow, it looked like a failed experiment.

However, it turned out that not all our cancer cells were rejected. The ones that had been engineered to overexpress Semaphorin 7A survived. We thought this protein would result in more lymph vessels, but what we learned is that it dampens the immune system in a way that can help cancer grow. Now we have a grant from Cancer League of Colorado to figure out how. And we think that Semaphorin 7A – this protein whose effect we stumbled onto purely by chance – might actually be a marker for patients who will benefit from immunotherapy.

C

omputer crash. Mistaken identity. Experimental error. Roundabout personal connections. Unexpected results. Most scientists try to avoid these things that can derail the direction of their work. And for the most part, they’re successful – experiments usually go according to plan and careers are usually linear things driven by interests, talents and (very, very) hard work. When things go wrong, the focus is on how to make them go right and coincidental connections can seem like distractions.

It takes a special scientist to follow coincidence into the unknown. But here’s the thing: The process of science can find answers to important questions, but sometimes it takes the process of serendipity to know what to ask. When life and luck combine to derail science, sometimes scientists end up riding new rails to important new places they never would have discovered on their own.

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9 C3: WINTER 2017

A CONVERSATION WITH KIAN BEHBAKHT, MD Professor, University of Colorado

B Y E R I K A M AT I C H

T RE VR ME RC H ANT

School of Medicine Director, Division of Gynecologic Oncology, Gynecologic Oncology Fellowship Program

Twenty years ago, Kian Behbakht, MD started researching ovarian cancer at a time when

C3: Are there ways to find ovarian

there was not much hope for women diagnosed with the disease. Here he talks about

cancer earlier?

how growing awareness for the condition has brought new resources that have helped

Behbakht: A major challenge in ovarian cancer

drive the pace of discovery.

diagnosis is the fact that medical technology doesn’t allow us to survey the abdominal cavity

C3: What is the biggest advantage

C3: Has research changed along

repeatedly without surgery. The moment technol-

of working at CU Cancer Center?

with treatment?

ogy allows the detection of circulating tumor cells

Behbakht: Without a doubt, collaborators and

Behbakht: The paradigm shift in the way we treat

or some sort of scan that can detect changes from

infrastructure. When I first arrived in 2002, my

ovarian cancer gives us the unique opportunity to

the outside, screening could help us catch this

lab was near Heide Ford’s (CU Cancer Center’s

study the tumor and its environment before and

cancer sooner.

Associate Director of Basic Research) and I knew

after chemotherapy. Until recently, our approach

she was looking at various genes in breast cancer.

had been static – we would gather information

We started working on developing drugs similarly

through genomic testing and maybe immune

targeting genes in ovarian cancer. Andrew Thorburn

analysis to plan treatment but we wouldn’t have

(Professor of Pharmacology) joined us in studying

the opportunity to revisit the biology of patients’

a gene called SIX1, which is active in embryonic

tumors after treatment. We have just gotten funding

development in making cells grow while at the

to gather dynamic data, before chemo and after

same time stopping the cells from dying. Cancer

three cycles of chemo, from a starting group of

cells sometimes reactivate this embryonic pathway

10 patients to see what we can learn. This sort of

to drive their own growth and survival. For the past

data is not available in ovarian cancer and this is a

15 years, our group has worked to find treatments

unique opportunity to study the before and after in

based on this.

a patient setting. What we find may have implications in the way we think about treating other types

C3: Has the approach to treating ovarian

of cancer.

cancer changed over the years?

Behbakht: Recently the way we approach it

C3: What challenges do you think lie ahead

has changed dramatically. It used to be “take no

for ovarian cancer research?

prisoners.” Remove everything. Today we have

Behbakht: National collaborative grants put me

a more thoughtful, methodical approach. We do

where I am today and the exciting advances of the last two years are a result of the research invest-

a laparoscopy, take samples, look around. If we cannot remove the tumor completely, we give three

C3: When did ovarian cancer patients

ment 20 years ago. However, if the current funding

cycles of chemotherapy and come back when

start to live longer?

environment continues, we risk losing steam and

we have a better chance of a successful surgery.

Behbakht: There has been some progress over

the ability to move forward for the next 20 years.

This approach also helps us eliminate unnecessary

the previous decade, but only in the past two

Because much of what we learn from ovarian

biopsies and interventions.

years have we seen major developments. Targeted

cancer research is applicable to other cancers,

therapies and new uses of chemotherapy have

lack of funding for research into this cancer type

dramatically improved treatment options, helping

could affect our inroads against the disease as

to push median survival past five years. We want

a whole. That is a sobering thought.

to continue building on that to allow women and their families more time for important future life events, for example another wedding or another grandchild. Every year that we get a few more percentage points in overall survival is another year of progress toward making this a chronic disease women can live with.

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CLINICAL

CARE C U C ANC E R C E NT E R

MD In Breast Surgery, Sometimes Less is More G R ETC H E N AH R E N DT LEAD S B R EAST C E NTE R I NTO NATI O NAL S P OTLI G HT

BY GA RT H S U N D E M Last year when surgeon Gretchen Ahrendt, MD,

on the faculty of the University of Rochester in New

was considering a move from the University of

York, Denver won’t be the snowiest place Ahrendt

Pittsburgh to accept the position of Director of the

has lived…but the fact that snow can exist under

Diane O’Connor Thompson Breast Center on the

a blue sky might come as a shock. Somehow,

Anschutz Campus, she and her husband, Steven

though, we’re pretty sure that Gretchen Ahrendt

– also a surgical oncologist – agreed their three

and her family will fit in just fine here in Colorado.

daughters would have to support the move.

“Even though we’re empty-nesters now, we

And while she’s in town, Ahrendt hopes to continue growing the Diane O’Connor Thompson

didn’t want to leave Pittsburgh and leave them

Breast Center into a nationally recognized leader

without a home,” Ahrendt says.

in breast cancer research and care.

The girls couldn’t believe their good luck.

“Our program is already exceptionally strong

GRETCHEN AHRENDT, MD Director, Diane O’Connor Thompson Breast Center

Ever since they were little, the family had escaped to

for young women with breast cancer, in large part

the mountains whenever they could. When Ahrendt

due to the work of Virginia Borges, director of

moved to Denver in May, the girls scored a home

the Young Women’s Breast Cancer Translational

base in one of the best mountain recreation cities

Program, and I’m very interested in helping the

in the world.

program focus on the continuum of breast cancer

brings expertise in a relatively new technique in

across age,” Ahrendt says.

which small “seeds” are implanted into the breast

“When they were here this summer, we hiked in Rocky Mountain National Park and went up

As a surgeon, it may seem counterintuitive that

Pike’s Peak. One of my daughters was just here for

one of her main goals is to evaluate situations in

a three-day weekend and we mountain biked on

which patients may need less surgery.

Saturday, hiked a 13er on Sunday and went kayaking on Monday,” she says.

“Most people know about drug clinical trials,

The bigger goal is to go beyond treating cancer, to treat patients with cancer.

“At Carleton, I got really involved in the Chemistry Department – tutoring, grading papers

out my career I’ve had a special interest in trials that

and doing summer research – but I went into

compare the results of more versus less surgery,”

medicine because I wanted to connect with

she says. Currently the Center offers a trial compar-

people,” Ahrendt says. “Working in breast cancer

ing more versus less lymph node surgery. Soon

sort of marries the best of surgery and medicine

Ahrendt expects to open a trial exploring whether

– you have an immediate, tangible impact on

women whose breast cancer responds dramatically

patients, but then you get to follow them for a long

to chemotherapy may omit surgery entirely. “If a

period of time.”

Ahrendt points out that the growth of the

the question whether there’s any role for surgery

UCHealth system will allow her to reach even

at all. In many cases, surgery plays an essential

more patients.

role, but we’re starting to learn more about when it doesn’t,” she says.

C/O G RETCHEN AHREND T

to pinpoint tumor location, size and orientation.

but there are surgical clinical trials too, and through-

tumor melts away with chemotherapy, this trial asks

In addition to reducing complications and recov-

This winter, Ahrendt – who ran cross-country

Professor of Surgery, CU School of Medicine

“As a physician, first and foremost, most of us go into medicine because we care about connecting with people and improving their lives,” she says.

ery times, making treatment easier on the body

“You can do that one-on-one, but developing a

may allow doctors to treat older or more fragile

program and leading a program lets you connect

patients. When surgery remains necessary, Ahrendt

with so many more. Here in Colorado, we have

hopes to implement cutting-edge technologies to

a chance to get out into the community to reach

maximize effectiveness while minimizing the impact

more women and bring services only an academic

at Carleton College in Minnesota – is looking

on patients’ lives. For example, she points out that

medical center can offer.”

forward to downhill and cross-country skiing.

small breast tumors are often marked for surgery

After Pittsburgh, PA, Northfield, MN, and 5 years

by a wire. “It’s not terribly precise and patients dislike it,” she says. Instead of this wire, Ahrendt

11 C3: WINTER 2017

TAY LOR ABARC A

W H E N T H E S TA R S A L I G N L A B W O R K AT C U L E A D S T O L I F E - S A V I N G C L I N I C A L T R I A L F O R R E T I R E D M A R I N E , R I C H A R D B E R G E R

“I have had a good life.”

They’re the words of someone who believes they are nearing the end.

This is exactly what Richard Berger, husband, father, grandfather and 27-year Marine Corps veteran, said to his family as they sat in a hospital room on the 11th floor of the University of Colorado Hospital on a sunny morning in late March of this year. “I have had a good life,” he continued,

“But I am really not ready to die yet.”

BY TAY L O R A B A R C A

12 WWW.COLORADOCANCERCENTER.ORG

A SU D D E N C HAN G E Richard Berger had been active all his life so when he suddenly got sick during a ski trip in Snowmass, Colorado at the beginning of 2017, he knew something was not right.

“It all happened so fast. I just started feeling really bad. As we were walking down the street to go see a concert I just got sicker and sicker to the point where I had to run behind a truck and got physically ill,” says Richard. “I turned to Karen and said we have to get out of here.”

“Fast” is an understatement. Just two days earlier, Richard and his wife Karen had been skiing blue runs like Sneaky’s off Snowmass’s Big Burn chairlift. Now he couldn’t keep his picnic down and getting to his car just a couple blocks away was a struggle.

“I knew it was bad when I heard Richard say he felt weak,” said Karen. “We have been married for 50 years and I have never once heard him say he felt weak.”

They decided to go to a local urgent care.

“It seemed like I had a stomach flu but what caught the doctor at the urgent care off-guard was how quickly my temperature was fluctuating,” said Richard. “He simply said to me ‘you don’t have the flu’ and sent me to Glenwood Springs for more testing.”

N OT TH E F LU Later that evening, blood tests showed abnormal myeloblasts.

In medical terms the suffix “-blast” is a way to label stem cells that have not yet matured into whatever cell types they will eventually become. In Richard’s case, these immature myeloblasts should have developed into white blood cells but instead were stuck in limbo, replicating out of control. By 9:30pm that evening Richard had been diagnosed with leukemia.

“We had heard of leukemia before but didn’t know much about it,” said Richard. “It wasn’t until later that I discovered the type of leukemia I have, acute myeloid leukemia or AML, was the one of the worst types. It was then we realized what we were up against.”

After an uneasy night in Glenwood Springs the Bergers had a difficult choice to make: Should they fly home to North Carolina?

“I remember the doctor saying very clearly that if I wanted to live I should head down to the Anschutz Medical Campus in Aurora,” said Richard. “He had ordered the ambulance and was sending me to a doctor who was conducting a study for people with AML.”

T H E STAR S ALI G N E D When Richard arrived at the University of Colorado Hospital he was, in his own words, “as sick as a dog.” His white blood count, neutrophils, and hemoglobin levels were all next to nothing. The counts meant that the tiniest infection that would be a nuisance to anyone else would have meant a very rough road for Richard.

Over the next few days he met with a team of doctors that included CU Cancer Center investigators Daniel Pollyea, MD, MS, clinical director of Leukemia Services at the CU School of Medicine, and Jonathan Gutman, MD, clinical director of Allogeneic Stem Cell Transplantation at University of Colorado Hospital. After a few more tests, they told Richard that he was a good match for a clinical trial of a new AML therapy being tested at the Cancer Center.

“We feel like the stars truly aligned for us to have ended up at one of only 25 locations in the entire world that was doing this clinical trial,” said Karen. “If we would have chosen to get on that airplane back home to North Carolina we could be facing a much different situation.”

Richard’s treatment consisted of four, week-long rounds of chemotherapy along with a new experimental drug called venetoclax, which was developed in part at the CU Cancer Center in a collaboration between Pollyea and Craig Jordan, PhD. “Back in 2013 Craig published an important paper showing that leukemia stem cells over-express a protein called BCL2,” Pollyea says. “He suggested that inhibiting BCL2 might be an effective therapy to eradicate leukemia stem cells, the root cause of AML. Several companies have had various BCL2 inhibitors but venetoclax is the most specific, almost exclusively hitting BCL2 so that patients can avoid symptoms from off-target effects. Based on Craig’s work, we did a pilot study of venetoclax as a single agent in patients with relapsed AML. That worked well enough for us to design a trial combining the usual AML chemotherapy, azacitidine, with venetoclax for newly diagnosed AML patients. The results have been extraordinary. We strongly believe this is one of the most important developments in AML in many years.”

“Before my diagnosis I had faced death at least five times in hostile situations in Vietnam and other parts of the world,” Richard explains. “I told the doctors ‘let’s do what we have to do’ and that has been my mentality throughout this process.”

A “D EV I L D O G” TH R O U G H AN D TH R O U G H Richard trained this “do what we have to do” mentality during a lifetime serving the United States. He joined the Marines in 1966 at just 22 years old. At that time, he had no idea that he would be involved in multiple wars, including Vietnam and the Gulf War, or that he and his family would be moving as often as they did.

“My God, we have lived in so many places,” Richard says.

“We started out in California, then moved all over including 29 Palms. Then New York, Virginia, Japan, Florida, Washington DC, Germany, Hawaii, North Carolina and part-time in Colorado.”

It was not always easy for the Bergers – Richard was away a lot (most) of the time even when he and Karen had two small children, Kelly and Charlie, at home. But they always made the best of their experiences.

13 C3: WINTER 2017

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R I C H A R D B E R G E R W I T H H I S B E L O V E D C A R E T E A M AT A N S C H U T Z . H E C A M E T O T H E C U C A N C E R C E N T E R F O R A L L H I S B L O O D T E S T S .

“When the children were younger we lived in Okinawa, Japan.

When they were older we lived in Germany and saw the Berlin Wall come down,” said Karen. “It was such a great experience for the whole family to be immersed in different cultures.”

In 1992 Richard retired from the Marine Corps and started working for Sprint as the director of Managed Network Services.

Later he was named president of the McGhee Foundation, a non-profit organization in Virginia which provides a community venue for educational and cultural programs in history, horticulture, agriculture and the arts. He is also a volunteer firefighter in North Carolina.

“It’s been a crazy life,” Richard said. “But I would not have traded it for anything.”

A C O LO R AD O R E C OVE RY As it turns out, the unpredictable lifestyle the Bergers led ended up helping them during Richard’s treatment in Colorado.

“To be on the trial we had to commit to live in Colorado,” says Karen. “I think the doctors were shocked by how quickly we agreed but it was no big deal for us. Moving is what we do!”

After two weeks on the eleventh floor of University of Colorado Hospital, the couple ended up living in a house they rented on Airbnb just minutes away from the hospital for a month. Once they got the go-ahead from Richard’s care team, they moved up to the cabins they had been restoring near Boulder that belonged to Karen’s grandparents.

“The cabins were a great place to recover,” said Richard.

“They are quiet, beautiful, and a place where it is easy to control my environment, which was important during my recovery.”

Although Richard got the OK to do his blood tests in Boulder, the couple felt strongly about going to their beloved care team at Anschutz for all of his tests.

“We will happily drive down three times a week to see the people we have grown to love,” said Karen. “We truly have never experienced care like we do here.”

14 WWW.COLORADOCANCERCENTER.ORG

G ETTI N G STR O N G E R For Richard, the combination of the two drugs has been a life-saver. Literally.

“I have had no side-effects and take four pills once each morning,” he says. “I am getting stronger and back to normal each day. It truly is a day-and-night difference from where I was in March. I truly believe getting on the trial saved my life.”

Just a mere seven months after diagnosis, Richard is in remission.

“A couple days ago I was able to bench 100 pounds five times at the gym!” he says. “It’s not where I used to be, but it’s a lot better than where I’ve been.”

In June, Richard and Karen celebrated their 50th wedding anniversary, something that in March they were not sure they would be able to do. Recently, they were able to move back to North Carolina sooner than they thought, but they still fly out once a month to meet with Dr. Pollyea, have blood tests and refill the prescription of his life-saving study drug.

“Some people might think it’s a hassle,” said Richard. “It is absolutely the opposite. I would not want to be anywhere else.”

Richard and Karen are highly complimentary of the entire staff on the 11th floor and the BMT and Cancer Center teams.

“They were all professionals, responsive to my needs and extraordinarily helpful when I needed help the most. I am honored to go visit all of them at the hospital when we’re in town and consider them my good friends!” says Richard. “As for Drs. Pollyea, Gutman, and Jordan, they are, perhaps, three of the finest, most dedicated men I have ever encountered. They saved my life.

As a Marine Colonel, now retired, I am proud to salute them!”

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

ST RY INSIDE

Targeted Treatments Against Acute Myeloid Leukemia

Venetoclax

Mylotarg

1986 Gene BCL2 identified as

1989 Study shows that AML

key player regulating cell death

cells are often marked by the

Midostaurin

Idhifa

protein CD33

1996 BCL2 expression shown to

1991 Development begins of

1996 Study finds FLT3 gene

predict poor prognosis in leukemia

“antibody-drug conjugate” gem-

mutation in 35 percent of

tuzumab ozogamicin, designed to

AML patients

1990s

1980s

For AML and many cancers, laboratory work done decades ago is now fueling a boom in new medicines targeting the genetic quirks of each cancer subtype. With new technologies, new awareness, and now a path paved by the first generation of successful targeted therapies, the pace of innovation against cancer is accelerating!

target AML cells expressing CD33

1997 Phase 2 clinical trial begins for gemtuzumab ozogamicin, now named Mylotarg, against relapsed AML

2000 FDA approves Mylotarg

2002 Drug PKC412 shown

2009 Drug AG-221 developed

for patients over age 60 with

to inhibit the action of mutated

to target IDH2 mutation, seen as

relapsed AML

FLT3 gene

a possible target in brain cancers

2000s

2008 Early BCL2 inhibitors are tested but are found to be unsafe

2002 PKC412 is renamed Midostaurin and enters phase 2 clinical trial against AML with

2010s

FLT3 mutation

2013 BCL2 inhibitor reengineered

2010 FDA withdraws Mylotarg

2015 Midostaurin finishes

2010 Study finds IDH2

for safety and named ABT-199

due to safety concerns

successful phase III clinical trial

mutation in AML

2013 The CU Cancer Center lab

2017 FDA re-approves Mylotarg,

2017 FDA approves Midostaurin

2014 AG-221 is renamed

of Craig Jordan, PhD, finds the

this time requiring that it be

to treat AML with FLT3 gene

Enasidenib, is granted FDA

protein BCL2 over-expressed in

matched only with patients whose

mutations

fast-track status against AML

leukemia stem cells

AML cells over-express CD33

with IDH2 mutation

2014 ABT-199 enters phase 1b

2017 Enasidenib renamed Idhifa

clinical trial against AML

and earns FDA approval against AML with IDH2 mutation

2016 ABT-199 is renamed Venetoclax and earns FDA approval against CLL

2016 Venetoclax enters phase 1/2 clinical trial in older AML patients

2017 (July) FDA grants Venetoclax “Breakthrough Designation” for use with older AML patients

15 C3: WINTER 2017

DRE W H AY E S

E

LIPSING

the Sun

BY D E B RA M E LA N I

CU CANCER CENTER PROGRAM TARGETS YOUTH ATTITUDES, BEHAVIOR WITH AIM OF

Reducing Skin Cancer

A

chorus of “Whoas!” and “Wows!” filled the classroom, as a group of wide-eyed middle-schoolers peered at the eight once-colorless beads they had strung on a pipe cleaner not long before. After smearing sunscreen on four of the beads and running outside with their creation, exposing it to the sun for just 20 seconds, the students filed back in, finding their four unprotected orbs had taken on red and purple hues. Levi Bonnell, one of their hands-on activity leaders, explained that the special beads were solar-radiation sensitive, just like their skin.

“I’m going to start wearing sunscreen now,” some students vowed, as they observed the stark contrast between the bare beads and the sunscreen-slathered beads, which remained colorless.

Recalling his experience with the pilot CU SunSmart program in Aurora’s East and North middle schools last spring, Bonnell, now a researcher at the University of Vermont, says it was inspirational and rewarding. “I think if I had participated in this project during my master degree program, I might have switched courses in my career to more of a nonprofit or public-health side,” said Bonnell, a University of Colorado Master of Public Health graduate.

Slaying a State Specter

As skin cancer rates continue a relentless 30-year climb, striking at younger ages and outnumbering all other cancers combined, changing Colorado youth behavior is critical, says Myles Cockburn, the CU Cancer Center’s program co-leader for prevention and control who launched the SunSmart program. This year, Cockburn’s students could reach as many as 55 classrooms, including some Denver public schools.

16 WWW.COLORADOCANCERCENTER.ORG

“Colorado has among the highest skin-cancer rates in the country,” says Cockburn, who developed a SunSmart program in Los Angeles while working at USC, which he hopes to partner with the CU program. High altitude and outdoor-recreation rates contribute to the elevated incidence, which is as much as 30 percent higher than the national average, according to the Colorado Melanoma Foundation. “So it’s obviously a good place to do skin-cancer prevention,” Cockburn says.

By combining service-learning and research, the program’s ultimate goal is to prove that changing youth behavior reduces rates of skin cancer. Meanwhile, CU students advance research, learn public education skills, serve as role models for youth pondering health careers, and, most importantly, teach sun safety in the surrounding university community.

Targeting Colorado’s Youth

There are many types of skin cancer. Although their seriousness varies, all require treatment. On one end of the spectrum, basal cell carcinoma grows slowly and is rarely fatal. The most common form of skin cancer, basal cell might be looked at as an unpleasant and expensive nuisance, Cockburn says. On the other end of the spectrum is melanoma, the deadliest of skin cancers, which becomes rapidly invasive when left untreated.

“Melanomas metastasize quickly to your liver, your lungs and your brain, as quickly as any other nasty cancer out there,” Cockburn says. Colorado ranks among the highest in the nation for death risk from skin cancer, and a clear link exists between UV exposure during youth and melanoma in adulthood.

“We don’t really understand the biology that well, but I think that part of it is that your skin is still developing when you are

Although skin-cancer rates are much higher in the white population, Hispanic and African-Americans, who outnumber white students in the Aurora school district, are also seeing increased rates of skin cancer. What’s worse, possibly because of lack of awareness and lack of access to healthcare, the darker-skinned populations are more likely to die from it, Cockburn says.

“Our students need to be able to understand that even though we have more melanin in our skin because we’re African-American, it doesn’t mean that we are not able to get skin cancer,” says Fayette Augillard, college and career success coordinator for Aurora Public Schools, referring to the pigment responsible for skin darkening. “Being able to relay that to their parents is also important,” says Augillard, who says the SunSmart program works well with North and East middle schools, which have a health-career focus.

Cockburn hopes more parents will get the message, as research suggests parent engagement goes a long way toward shaping youth behavior. Toward this goal, the program’s CU student participants plan more handouts and homework this year. East Middle School teacher John Wolner says the addition of homework could have big implications for his students’ families. “I don’t think parents think about it either,” he says, adding that many of his students come from homes with multiple children and extended family members, and many parents work outside. “If everybody were educated, the skin-cancer chances would be lower.”

CU students participating in SunSmart have their work cut out for them. Cockburn and his L.A. colleagues found during their research that upwards of 70 percent of students reported having a sunburn in the past year, while fewer than 20 percent routinely used preventive measures, such as sunscreen. While a four-year observation with pre-and post-surveys of the young students found knowledge and behaviors did change for some, much room for improvement remains, he says.

But Bonnell, whose best friend growing up lost his mother to melanoma four months after diagnosis, says it’s a challenge worth pursuing. “It’s a devastating disease,” he says. “And kids don’t understand that choices they make as kids, in terms of skin protection, can ultimately affect them later on in life.

They’re a great group to target. And they’re learning science and having fun, too.”

EXPERT OFFERS SUN-PROTECTION TIPS FOR PARENTS CU Cancer Center’s Myles Cockburn, recognizable as the man on campus who always sports a wide-brimmed hat and long-sleeved shirt regardless of the forecast, takes no chances with the powerful sun. Below, he addresses some common parent misconceptions about sunscreen use.

MYTH: My dark-skinned child does not burn.

TARA URSO

Diversifying the Message

Altering Attitudes

FACT: Any time your skin gets darker, that’s your skin saying it’s had too much sun. If a child is dark-skinned, it may be that you just can’t see the red and the inflammation because their skin is a little darker to start with.

There is no such thing as anyone who doesn’t burn.

MYTH: We aren’t going to be in the sun long enough.

FACT: One thing that we do have a lot of data on is that people grossly underestimate how much time they are going to be outside.

And most people don’t bother re-applying sunscreen (which washes and sweats off, so should be applied frequently). A lot of ultraviolet radiation is also reflected off surfaces, so just because you are spending some time in the shade doesn’t mean you aren’t getting it.

MYTH: It’s winter. We don’t need sunscreen.

FACT: Interestingly, we are doing a study at the moment looking at where on the body people get melanomas in Colorado, and it looks like melanomas are most likely to occur around the head and neck region. We think that’s probably due to the number of people who are exposed to the sun from the neck-up while skiing! Certainly there’s less sun and less UV during winter, but there’s still some. And in fact when you are standing on the snow, you are getting at least as much reflected up off the snow as you are from the sun directly.

JEREMY THOMAS

young, up until age 10 or 12. So if you bombard it with radiation, which is what ultraviolet is, when it’s developing, you are much more likely to end up with a melanoma in adulthood,” Cockburn says. Simple math explains another factor: The more sunburns over the course of a life, the higher the risk of skin cancer, he says.

Focusing on pre-teens, who are old enough to understand the science and still young enough to listen, could help with a “really disturbing” increase in skin cancer in the early-20 age group, Cockburn says. Tanning behaviors, especially tanning bed use, are largely to blame for the young-adult cases, he says.

MYTH: There’s no history of skin cancer in our family so we don’t need to worry.

FACT: Family history is not a particularly big predictor of either melanoma or skin cancer, at least in terms of genetics. But behaviors and experiences tend to run in families – you might do the same things as your family. For instance, when my brother and I were growing up, we didn’t have sunscreen and we mostly went the same places together and had the same amount of sun exposure.

So we probably have a very similar risk of skin cancer just because of that. And that reinforces our message: The key to reducing skin cancer is changing behavior.

17 C3: WINTER 2017

S U P P O R T E R

F CUS

Funding Talent for the Future A PLU M B E R, A PATI E NT AN D H E R D OCTOR H E LP KE E P R E S EARCH STRONG I N COLORAD O GART H SUNDE M

BY GA RT H S U N D E M The relationship between Patricia Connor’s family and UCHealth started in 1941 when Patricia’s grandfather, John, a second-generation Irish immigrant, worked on the plumbing during the expansion of the Fitzsimons General Hospital. Then as an elementary student in the 1950’s Pat remembers being treated at Colorado General, as it was known, for a lazy eye. She went on to work as an Assistant Professor in the CU School of Medicine Child Health Associate/Physician Assistant Program in the 1980’s.

But the event that truly cemented the family’s

Photo caption here

relationship with this campus was Pat’s breast cancer diagnosis at age forty.

“I remember that my doctor came into the room, running late. He showed me the mammogram and pointed out what he called some ‘interesting architecture,’” Pat says. “I asked about a mass next to

Patricia Connor, left, with Dr. Viginia Borges, right

the area and that’s how the diagnosis started.”

Soon she had switched her care to William Robinson, MD, PhD, the Monroe and Rella Rifkin

at Harvard and work as an assistant professor at

Endowed Chair in Cancer Research in the CU

CU, Dr. Borges had demonstrated tremendous

plumber and continues through a relationship

School of Medicine Division of Medical Oncology.

promise and curiosity, spearheading trials of new

between a cancer patient and her doctor, now

Treatment included surgery, chemotherapy, and five

cancer immunotherapies, evaluating the role of

allows one of today’s top cancer researchers

years of maintenance therapy with the anti-estrogen

inflammation in breast cancer associated with

to continue her work of saving lives in Colorado.

drug Tamoxifen, which had just started to be used

changes in the breast after pregnancy, and defining

widely. Now over 20 years later Pat continues to

new hormones that drive the disease.

see Dr. Robinson for follow-up care.

Dr. Borges was such a bright light that

Academic research institutions depend on the

Dr. Robinson worried she would be recruited away.

talented doctors and scientists they are able to

Because of the excellent treatment and the hope

recruit and retain. In 2014, Dr. Robinson talked with

that the CU Cancer Center has given the Connor

Patricia about one of these promising physician/

family, Patricia had been looking for an opportunity

scientists, Dr. Virginia Borges, who treats young

to give back and now was her chance.

women with breast cancer. During her internship GARTH SUND EM

After working as a plumber, John Connor

WWW.COLORADOCANCERCENTER.ORG

Dr. Ginger Borges uses her position to lead the Young Women’s Translational Breast Cancer program at the CU Cancer Center where she is

tracting firm, allowing the family to start a foundation

able to offer young women promising treatments

with a mission that includes expressing gratitude to

years before they are available elsewhere.

Colorado for all it has given the family. The founda-

“My parents’ commitment was to do something

tion, which is named after John and his wife, Irene

that would have an impact in Colorado,” Pat says.

A Connor, is directed by a board that includes Pat

“My connection is with young women’s breast

and her two brothers Robert F. Connor, Jr and

cancer. I am honored that our interests can come

John Joseph Connor, II, and two of John Connor’s

together around Dr. Borges’ work at the University

great grandchildren.

of Colorado Cancer Center.”

and her brothers were able to create the Robert F. and Patricia Young Connor Endowed Chair in Young Women’s Breast Cancer Research, the position now held by Virginia Borges, MD.

18

Academic research institutions depend on the talented doctors and scientists they are able to recruit and retain.

became president of a successful mechanical con-

With the help of her family foundation, Patricia

The Robert F. and Patricia Young Connor Endowed Chair in Young Women’s Breast Cancer Research

So a family story that began with an Irish

N E W S

SOLD OUT DINNER IN WHITE SUPPORTS GI CANCER RESEARCH

TAY LOR ABARC A

C O M M U N I T Y

Every summer a secret location near the Denver Metro area is transformed into a slice of Paris for the annual Dinner in White event, benefitting CU Cancer Center. On August 19, 2017, nearly 300 people dressed in white, packed a picnic, and waited for TAY LOR ABARC A

the venue to be revealed – this year it took place at the 9th St. Historic Park on the Auraria Campus.

A 20-foot tall white Eiffel Tower set the stage for a taste of Paris in the Rockies. Upon arrival guests

INFINITE MONKEY THEOREM FUNDS

browsed a Parisian marketplace, picked from the wall of wine, played lawn games, used the photo booth,

SUMMER STUDENT FELLOWSHIPS

and listened to tunes from a local disc jockey, all beneath a 20-foot, pure-white Eiffel Tower.

The highlight of the evening was a heartwarming and inspiring speech presented by speaker Stephen

This summer, two students in the Cancer Research Summer Fellowship Program funded

Estrada. Stephen was diagnosed with stage 4 colon cancer at the young age of 28. When Stephen arrived

by CU Cancer Center had more than one thing

at the CU Cancer Center he was incredibly ill. After being placed on a clinical trial he began to feel better and

in common. Monica Weber and Madison Brown

more alive than he had for a very long time. Now, after being declared free of disease, his mission is to share

are both college undergraduates who focused

his story and raise awareness of young colon cancer.

their summer studies on colon cancer research.

And both of their fellowships were funded by Ben Parsons, owner of The Infinite Monkey Theorem,

ENDOWED CHAIR IN ESOPHAGEAL CANCER ESTABLISHED

an urban winery focused on making Colorado

When Katy Rady lost her brother, Paul R. O’Hara II to cancer, she turned her despair into an enduring tribute

wines in Denver’s RiNo district, who lost his

funding research at CU Cancer Center. We are honored to announce that Katy and her husband, also named

father to colon cancer in 2007.

Paul, have awarded $3.15 million to establish the Paul R. O’Hara II Endowed Chair in Esophageal Cancer

Every summer, the ten-week program gives

at the CU Cancer Center and to fund promising research in the search for a cure for esophageal cancer.

dozens of college undergraduates and more

Madeleine Kane, MD, PhD, CU Cancer Center member and professor in the CU School of Medicine,

advanced high school students the opportunity

led Paul’s care and is the first to hold the chair in his name.

to explore their interest in cancer research.

“My brother, Paul, and I shared the highs and lows and joys and sorrows of life,” Rady says. “His cancer

Brown and Weber spent their time working in

journey was grueling and heartbreaking and it was my privilege to be there for Paul. Dr. Kane was the

the labs of Todd Pitts, PhD, and John Tentler,

lifeline of hope that helped us get from day to the next.”

PhD, the associate director for education at CU

“This chair is the greatest honor of my professional career,” says Kane. “The Rady’s gift is emblematic

Cancer Center, director of the summer fellow-

of their love for Paul. Their amazing generosity will heighten awareness of esophageal cancer and improve

ship program, where they hoped to determine

outcomes for people with this disease.”

how a particular combination of cancer drugs combined TAK-228, which is an inhibitor of the mTOR pathway, with a MEK inhibitor called trametinib. Weber is combining TAK-228 with

TAYLOR ABARCA

works on colon cancer cells in the lab. Brown RECORD-BREAKING YEAR FOR CANCER LEAGUE OF COLORADO, AGAIN Cancer League of Colorado recently gifted

several inhibitors of diacylglycerol kinase in

$750,000 to CU Cancer Center to be used by our

order to block cancer cell metabolism.

physician/scientists for cancer research. This gift

“I have devoted my life’s work and business

is in addition to $150,000 that Cancer League has

ventures to honoring my father and those who

earmarked this year for the CU Cancer Center to

have gone through this battle. We are proud

fund certain investigator-initiated clinical trials.

partners of the University of Colorado Cancer

The latest research gifts are part of Cancer

Center and feel humbled to be able to assist with a fraction of their work,” Parsons says.

League’s annual fundraising record of nearly $1,100,000 and brings CLC’s fundraising total to almost $2.2 million in the last two years. CU Cancer Center projects funded in 2017 include improving targeted therapy in melanomas with BRAF fusions, enhancing the effects of immune checkpoint blockade with radiation therapy in head and neck cancer, and the CU Cancer Center’s Cancer Research Summer Fellowship Program.

19 C3: WINTER 2017

UNIVERSITY OF COLORADO DENVER

W I NT E R 2017

Non-profit organization U.S. POSTAGE PAID Denver, CO Permit No. 831

13001 EAST 17TH PLACE, MSF434 AURORA, CO 80045-0511

www.coloradocancercenter.org

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, Erika Matich Photos: Trevr Merchant and Casey Cass The CU Cancer Center Consortium Members UNIVERSITIES

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T H E

Back to Basics to Drive 21st Century Cancer Care

M E S S A G E

I

n 1971, President Richard Nixon signed the National Cancer

code of cancer cells. Other researchers had been picking apart

Act, declaring what came to be known as the “War on

the biology of the human immune system, with the harebrained

Cancer.” At the time, doctors were learning to use chemo-

idea that this knowledge could someday be used to turn the

therapies to attack the disease and it seemed like curing cancer was only as far away as the next wonder drug. Why would you invest in basic biology when the cure was so close?

However, despite some successes a cure for cancer remained elusive. What worked in some cases didn’t work in others and often even the cancers that initially responded

FROM THE DIRECTOR DAN THEODORESCU, MD, PhD

to chemotherapies eventually returned. It turned out that the equivalent of storming the beaches of Normandy was a poor model for attacking cancer.

machinery of the immune system against cancer.

It took decades of research with yeast and fruit flies and cell lines to build the basic knowledge of how cancer cells work.

One thing this research found is that we’re not really fighting “cancer” but “cancers”, each with its own genetic or genomic

“Sometimes you have to go back before you can go forward. And sometimes the fruit of a treatment that saves lives grows from the roots of basic research.”

Luckily, despite the early focus on clinical testing, there had

cause. This basic research has now paid off with a second great wave of clinical trials in which rather than blanketing cancer with chemotherapy, we are using molecularly targeted therapies to hit each cancer’s individual

Achilles heel. Even work on the immune system that for years

always been an undercurrent of people doing basic research.

seemed like such a pipedream is now paying off with extremely

Now as the first wave of clinical trials failed to find the prom-

promising immunotherapies against cancer.

ised cure, the field went back to this “drawing board” of basic research.

CU Cancer Center Founding Director Paul Bunn, Jr. was

Sometimes you have to go back before you can go forward.

And sometimes the fruit of a treatment that saves lives grows from the roots of basic research. Here at CU Cancer Center we

a product of this research-focused counterculture at the early

are hitting cancers from both directions, offering new therapies

National Cancer Institute. And he and his colleagues had a hunch

in clinical trials, while continuing to grow our understanding of this

where to look for the next wave of treatments: Inside the genetic

group of related diseases so that we can use this knowledge to grow the treatments of tomorrow.

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