C3: Collaborating to Conquer Cancer

COLLABORATING

TO CONQUER

CANCER A Newsletter for the University of Colorado Cancer Center | Anschutz Medical Campus

FALL 2010

Exposing Cancer’s Roadmap Leaving “the Las Vegas Effect” A Conversation Natalie Serkova, PhD Anschutz Foundation gives $1 million to cancer center expansion

CENTER NEWS

Garg

Oliver

Study pinpoints first lung cancer screening test Screening for lung cancer using low-dose “spiral” CT scans reduces lung cancer mortality by 20 percent compared to screening with chest X-ray, according to early results from the National Lung Screening Trial. UCCC was one of the trial’s largest sites.

“For the first time there is evidence from a randomized prospective clinical trial that low-dose screening chest CT results in a decrease in the number of deaths in people at high risk for lung cancer,” says Kavita Garg, MD, professor of radiology at the University of Colorado School of Medicine and University of Colorado Hospital. “We could save lives.

It’s just a matter of time until we get official guidelines for how best to use this tool.”

People with ALK+ lung cancer respond to new targeted treatment A study in the shows 57 percent of patients with ALKpositive advanced non-small cell lung cancer respond partially or completely to crizotinib, an investigational anaplastic lymphoma kinase (ALK) inhibitor.

In some cases, the cancer becomes undetectable in body scans.

UCCC member D. Ross Camidge, MD, PhD, one of the study’s authors, said UCCC

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Camidge

cares for one of the largest groups of ALK positive patients in the world. UCCC associate director Marileila VarellaGarcia, PhD, also a coauthor, developed one of the few ALK testing facilities in the world at UCCC. “By looking at lung cancer at the molecular level, we were able to find the patients most likely to respond to the ALK inhibitor and put them in this trial,” Camidge says. “Most patients feel better within days of beginning the drug in the trial and many have returned to active lifestyles with their cancer under excellent control.”

Theodorescu aids development of biomarker research standards An international group of 50 researchers, including UCCC Director Dan Theodorescu, MD, PhD, has published a paper on ScienceTranslationalMedicine.org that outlines standards for studying protein biomarkers in disease. This eminent group of researchers also has recommended that these standards serve as requirements for the reporting or publication of proteomic studies, ensuring that the essential elements necessary for replication and verification are in place.

“In order to provide usable data that will allow us to move forward in this field, we must address common shortcomings in the experimental design,” Theodorescu says. “We assert

Varella–Garcia

that successful studies generally use suitable statistical approaches for biomarker definition and confirm results in independent test sets.”

Oliver discovers new way to treat eye cancer, prevent blindness Rare but devastating, eye cancer can strike anyone at any time and treating it often requires radiation that leaves half of all patients partially blind.

But a new technique developed

by UCCC member Scott Oliver, MD, may change all that. Oliver has discovered that silicone oil applied inside the eye can block up to 55 percent of harmful radiation, enough to prevent blindness in most patients.

His findings, published in the July issue of the Archives of Ophthalmology, may revolutionize the way eye cancer is treated.

Theodorescu

Spillman

Estrogen therapy speeds ovarian cancer growth Estrogen therapy used by menopausal women causes a type of ovarian cancer to grow five times faster, according to a UCCC study published Nov. 1 in Cancer Research Menopausal estrogen replacement therapy (ERT) also significantly increases the likelihood of the cancer metastasizing to the lymph nodes, said the study’s author, UCCC member Monique Spillman, MD, PhD. The effect of ERT was shown in mouse models of estrogen receptor positive (ER+) ovarian cancer, which accounts for about 60 percent of human ovarian cancer cases.

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Get more UCCC news on our blog The University of Colorado Cancer Center has launched a new multiple-blog website: coloradocancerblogs.org. Subscribe to our blog to get Target: Cancer, a weekly post from a UCCC leader about what’s up in cancer research and treatment, and the latest news from UCCC, like these headlines: • Low-cost cervical cancer vaccine, developed by UCCC researchers, moves to human trials • UCCC researchers discover new leukemia pathway • Milk thistle shows promise for prevention of colorectal cancer in new UCCC study • Pre-treating bladder cancer cells increases chemotherapy effectiveness, UCCC lab finds • Colorado researcher Li discovers key mechanism for transforming adult cells into stem-like cells Go to www.coloradocancerblogs.org/subscribe today!

CONVERSATION

A Conversation With

Natalie Serkova, PhD Natalie Serkova, PhD, is associate professor in the Departments of Anesthesiology, Pharmacology and Radiology at the University of Colorado School of Medicine and the director of UCCC’s Core Facility for animal imaging and nuclear magnetic resonance. The lab provides services on all aspects of animal imaging for the University of Colorado, Colorado State University and Colorado School of Mines.

C3: What is physiological imaging and how is it different from other imaging in cancer?

Serkova: It’s much more detailed than the more commonly used anatomical imaging.

The goal of anatomical imaging—using technologies such as ultrasound, computed tomography (CT), magnetic resonance imaging (MRI) and position emission tomography (PET)—has been to see if cancer is present and then, after treatment, to see if it’s still present or changing. That kind of diagnostic isn’t good enough anymore.

Physiological imaging uses advanced imaging protocols (mostly MRI-and PET-based) to detect not only the size but also the specific characteristics of cancer: Is the tumor getting blood supply? Is it metabolically active—that is, taking a lot of nutrients from the blood?

Does it contain important diagnostic markers (such as HER2, which is found in breast cancer)? Previously we’ve answered these questions with biopsies—invasive and often painful procedures. Now we’re introducing these tumor-characterizing images into clinical radiological procedures.

Physiological imaging also helps us see how cancer cells are responding to new drug therapies.

C3: Your lab is one of only a few facilities in the country that provide both pre-clinical and clinical physiological imaging. Why are so few institutions doing this?

Serkova: For one thing, it’s very expensive.

We provide anatomical, physiological and metabolic imaging using various imaging modalities so the instrumentation for that is highly specialized and expensive. It takes a

great deal of effort to seek federal funding in order to be able to purchase and install MRI, PET and CT scanners, and we have to be successful at it.

C3: What sets your lab apart from other facilities?

Serkova: Modern imaging is highly complex and requires strong expertise in physics, engineering and cancer biology. We’re a comprehensive scientific and clinical team with technological, medical and biological backgrounds, so we bridge lab research and clinical care.

Also, most imaging scientists are trained as MRI or PET or CT specialists, but there’s growing interest in applying different imaging to get more information from the same cancer. I’m trained in all three areas, so I’m invited to speak at conferences where most attendees have one specialty. I can speak about the metabolic imaging research we’re doing using these different imaging protocols.

C3: How does small animal imaging, one of your subspecialties, contribute to the research?

Serkova: Before any procedure can be introduced into the clinics, we have to test it in animal models. Since imaging is non-invasive and doesn’t cause harm or pain, we can use it to follow the same mouse at different treatment points. We have our own animal radiology department for our small fourlegged patients that includes animal MRI, PET and CT scanners, which are similar but slightly smaller than clinical scanners. Once we establish which imaging protocol is the best to assess drug response in the mouse, we can apply the same protocols to the human patient treated with the same drug.

C3: What do you consider the most seminal work you have done?

Serkova: With our colleagues in medical oncology we’ve been able to assess the effectiveness of targeted drugs using MRI and PET scans. So, when radiologists see the patient under a particular treatment regimen, they know exactly which imaging protocol to use to see whether the drug is effective.

However, I believe our biggest success is yet to come. We now have a director of radiochemistry, which is unusual among leading institutions. It will allow us to create new radiolabeled molecules to further characterize and identify molecular targets in a particular cancer.

C3: What’s your long-term vision; what’s “the next big thing” in imaging research?

Serkova: The next big step for us will be in creating a comprehensive imaging center that will include all necessary components—such as pre-clinical imaging, clinical imaging, radiochemistry, bioengineering and advanced imaging analysis. The future in imaging is in developing a “personalized imaging” protocol for a specific patient using MRI and PET together to get a comprehensive “fingerprint” of each cancer patient.

We’ve already taken our first step by creating the Colorado Translational Research Imaging Center (C-TRIC). Now we have to work on making it successful.

Please Support UCCC: www.uccc.info/give.

Natalie Serkova, PhD: Associate Professor in the Departments of Anesthesiology, Pharmacology and Radiology at the University of Colorado School of Medicine and the Director of UCCC’s Core Facility for animal imaging and nuclear magnetic resonance

COLLABORATION

Exposing Cancer’s Roadmap

Synthetic lethal screens give UCCC researchers a bird’s-eye view to spot and stop secondary cancer pathways.

Story by Michele Conklin, Photos by Glenn Asakawa 4 | C3: FALL 2010 | www.uccc.info/c3

COLLABORATION

Aik-Choon Tan stood outside a hospital room in Baltimore five years ago feeling helpless. The 28-year-old computer scientist was devoting his career to developing complex algorithms to help ferret out the workings of cancer genes. Yet, his work meant nothing to the fouryear-old girl inside who was dying of cancer.

“It was a moment that really changed my view,” says Tan, PhD, now assistant professor of bioinformatics and medical oncology at the University of Colorado School of Medicine (SOM). “My old goal was to invent algorithms that got published. Now I want to do something that can apply to real patients.”

At the time, Tan was working at Johns Hopkins University. His minister had asked him to come to the hospital to translate for a Vietnamese family whose daughter was sick. Tan, who grew up in Malaysia and speaks four languages, did not learn until reaching the hospital that the girl was in her final hours.

“I had been trying for three years to get researchers to use an algorithm that I had developed,” Tan recalls. “I kept asking for more and more data, but I didn’t realize until that moment that every data point was a patient who had cancer.”

Tan soon followed several Hopkins teammates to the University of Colorado Anschutz Medical Campus in Aurora in search of a culture where computer scientists, laboratory researchers and physicians work side by side to translate laboratory research into patient treatment as fast as possible.

Earlier this year, a UCCC research team did just that when they screened the entire human genome and found the pathway that allows a particular type of leukemia cell to evade chemotherapy.

Working in mice, the team was able to block the pathway with a common organ transplant drug so that chemotherapy could kill the leukemia cells. Because the chemotherapy agent and the organ transplant drug are both already used in humans, the study is ready to move into clinical trials with patients. This happened in just four years, compared with the 10 or more years it typically takes to get a new drug to clinical trials.

“Cancer cells are very complex and have alternative paths that can be activated if you knock out the primary pathway,” says James DeGregori, PhD, co-leader of UCCC’s molecular oncology program, who led this work. “We now have a method of identifying those secondary pathways.

And, in many cases, drugs are already available that target them.”

“We’re hoping a one-two punch knocks it out,” DeGregori says. “But we may need punch three or even four. The beauty of screens is that they allow us to keep marching through.”

Searching every gene The technology DeGregori’s group used is called synthetic lethal screens, a technique that allows scientists to quickly determine which drugs are effective against selected genes. Thanks to the unique combination of talent and technology, the group’s work quickly gained momentum, and UCCC researchers developed an even faster and more accurate screening.

Using algorithms designed by Tan’s bioinformatics team, the UCCC synthetic lethal screen allows researchers to: • Screen the entire genome at one time. In the past, researchers could screen up to 10 genes at once, which took two or three months. Using this new tool, UCCC researchers now can screen the entire human genome—20,000 genes—in three months.

• Screen the genome in combination with a drug. UCCC’s screen identifies genes that become important for cancer cell survival only in the presence of the drug that is meant to kill the cells.

• Screen the genome for multiple research trials on multiple cancers at one time. UCCC researchers can screen the genome for multiple studies concurrently, slashing research time and costs.

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COLLABORATION

“This is the first time in history that we have the technology that allows us to investigate every gene at the same time in response to a drug,” says Joaquin Espinosa, PhD, assistant professor of molecular, cellular and developmental biology at University of Colorado at Boulder (MCD Biology) and co-leader with DeGregori of UCCC’s molecular oncology program.

UCCC partnered with programs at the University of Colorado at Boulder to develop the Functional Genomics shared core service, including the Espinosa Lab, the Colorado Initiative in Molecular Biotechnology (CIMB) and Molecular, Cellular and Developmental Biology (MCD Biology). The Colorado Governor’s Office gave CIMB a grant that the program used to buy the expensive 2,000-sample shRNA libraries necessary to perform the screens. MCD Biology contributed lab space and UCCC provided funding for staff.

Dr. Aik-Choon Tan combines computer programming with genetic data to find new druggable targets in cancer cells.

Because of this effective collaboration and use of funds, researchers throughout Colorado now have access to the technology through the jointly supported service.

“An individual lab could never afford to do this on its own,” says Espinosa. “We’re leaders in this approach because the Cancer Center and Boulder came together.”

Landing the knock-out punch To understand how the technology works, DeGregori suggests thinking of cancer cells as rebels who are using a bridge to invade a village—in this case, the patient’s body. Drugs such as chemotherapy knock down the bridge, but the rebels are ingenious and find other ways into the village.

Until now, researchers were stuck at ground level destroying only the paths they could see. The synthetic lethal screen provides researchers with an aerial view from which they can survey the entire human genome to spot the alternative pathways.

Dr. Joaquin Espinosa runs the shRNA facility, which uses a 2,000 sample library to conduct the screens.

Chris Porter, MD, assistant professor of pediatrics at the SOM and a pediatric oncologist at The Children’s Hospital, will lead the upcoming leukemia clinical trial that will treat patients with standard chemotherapy and the organ transplant drug.

“Before you might focus on a particular gene that you thought was interesting,” he says. “Now, it’s like looking from above and finding targets in a way that is not biased toward what you know.”

The leukemia study looked at acute lymphocytic leukemia and chronic myeloid leukemia that are caused by a genetic mutation resulting in an abnormal protein, called “Bcr-Abl.” When diagnosed early and treated with drugs that inhibit Bcr-Abl, CML is controlled in more than 80 percent of patients. However, drug response is unsatisfactory in the remaining 20 percent of patients, and the leukemia may relapse.

The synthetic lethal screen, developed by DeGregori lab member Mark Gregory, PhD, identified the genes that were keeping the leukemia cells alive. These genes act in an alternative pathway, called Wnt/NFAT. When this path is inhibited with the organ transplant drug, leukemia cells become more vulnerable to chemotherapy.

“We’re hoping a one-two punch knocks it out,” DeGregori says. “But we may need punch three or even four. The beauty of screens is that they allow us to keep marching through.”

Dr. Chris Porter is on the brink of opening a clinical trial for a new leukemia treatment found by a synthetic lethal screen.

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COLLABORATION

Finding new synthetic pathways and existing drugs that target them using synthetic lethal screens could drastically cut the time it takes to move new therapies from the lab to patients by eight years or more. The new leukemia therapy, for example, will move into early phase clinical trials just four years after the discovery was made in the lab and only a year after the screen was finished.

“In the past, the only discoveries being made were the obvious stuff,” DeGregori says. “The whole universe of possibilities is so greatly enhanced with these screens.”

Billions of data points

With the success of the leukemia study, other UCCC researchers are lining up to use the screen technology. Tan and his team are currently involved in 14 different studies.

Tan’s office is now embedded with other cancer researchers. He now works daily with cell biologists, molecular biologists and clinicians— all driven by personal stories just as compelling as his—to find effective cancer treatments as quickly as possible.

“We have the real potential to make a difference,” says Tan, his voice laced with optimism.

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The key to navigating this universe is the bioinformatics. Tan and his team must write complex computer programs that translate billions of data points into a format that researchers use to determine which genes are important targets.

“The mapping of the human genome plus these shRNA libraries allow us to take a drug that is not working and ask which of the 20,000 genes is affecting its function,” Espinosa explains. “But we couldn’t do this work without the bioinformatics.”

Screening the Genome University of Colorado Cancer Center researchers are ready to use the new synthetic lethal screen tool to answer biologic and therapeutic questions about cancer. The research includes: • Detecting genes that help acute myeloid leukemia cells survive standard chemotherapy and finding agents to drug them (Chris Porter, MD, UCCC Developmental Therapeutics Program; James DeGregori, PhD, UCCC Molecular Oncology Program co-leader; and fellow Mark Gregory, PhD) • Identifying genes and pathways that help “nutraceuticals”—food or food products that can prevent diseases like cancer and provide other health benefits—work in prostate and head/neck cancers.

(Rajesh Agarwal, PhD, UCCC AMC Cancer Prevention & Control Program co-leader; and Robert Sclafani, PhD, UCCC Cancer Cell Biology Program co-leader)

2,000 shRNA samples are kept in two freezers near Espinosa’s lab at CU-Boulder.

• Looking for different ways colon cancer becomes resistant to targeted therapy as well as drugs that can be combined with standard chemotherapy to bypass the resistance process. (S. Gail Eckhardt, MD, UCCC senior associate director and Developmental Therapeutics Program co-leader; UCCC Developmental Therapeutics Program members AikChoon Tan, PhD, and John Tentler, PhD; and GI cancer researcher Todd Pitts, MS, and Joaquin Espinosa, PhD, UCCC Molecular Oncology Program co-leader.)

• Understanding mechanisms of melanoma resistance to BRAF inhibitors, a breakthrough therapy that seems to lose effectiveness after six months, and another chemotherapy agent. (David Norris, MD, UCCC Developmental Therapeutics Program and Yiquin Shellman, PhD, UCCC Cancer Cell Biology Program) • Uncovering how the protein Six1 creates resistance to TRAIL-mediated death in

breast cancer. (Heide Ford, PhD, UCCC Hormone Related Malignancies Program co-leader; Andrew Thorburn, PhD, UCCC deputy director; and Kian Behbakht, MD, Hormone Related Malignancies Program) • Identifying genes whose inhibition sensitizes head/neck, and lung cancer cells to EGF, FGF and ALK receptor inhibitors and causes relapse. (DeGregori, Tan, and Paul Bunn, MD, Robert Doebele, MD, and Lynn Heasley, PhD, UCCC Lung/ Head & Neck Cancer Program) • Pinpointing genes that determine whether cancer cells die in response to activation of p53, the tumor suppressing gene that is mutated in most cancers. (Espinosa) • Looking for pathways that allow bladder cancer cells to metastasize to the lung in the presence of newly discovered compounds that are part of the Ras signaling pathway. (Dan Theodorescu, MD, PhD, UCCC director)

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CLINICAL CARE

Leaving “the Las Vegas Effect” of Conventional Prostate Cancer Treatment

By Mary Lemma

By his own account, Dr. Al Barqawi is “a simple man.” But simple or not, he’s a man on the cutting edge of treating prostate cancer— without actually cutting anything.

In 2009, Barqawi adopted a technique he observed during treatment of a deep-brain tumor. If his colleague at the University of Colorado Hospital could “zap” the brain tumor without damaging nerves around the eye, he wondered why couldn’t the technique be applied as successfully to treat cancer of the prostate?

“It’s not rocket science,” Barqawi insists, yet the focal-laser treatment he has deployed on early-stage cancer patients relies on highly sophisticated 3D mapping technology to precisely locate the cancer.

He then uses a laser to “fry” the tumor.

“When you’re talking about cancer, ‘gambling’ is an ugly word.”

~ Dr. Barqawi

A pioneering surgeon with a ready metaphor, Barqawi sees focallaser treatment as a viable alternative to “the Las Vegas effect” of conventional approaches to prostate cancer, which will affect one man in six during his lifetime.

“With prostate cancer, there have been two options: overtreatment or undertreatment,” Barqawi says. Surgery is invasive and, while it may be the only known option for patients in advanced stages of the disease, there are side effects to consider: urinary complications, incontinence and erectile dysfunction—effects that also carry a psychological burden.

Barqawi says about two out of three men newly diagnosed with prostate cancer potentially fall into the “overtreatment” category.

“For every 10 men who undergo radical treatment,” he says, “eight

or nine didn’t need it to survive. A lot of people buy big cars when they don’t need them.”

And with watchful waiting, which ostensibly has no risk, you’re still risking undertreatment, he says.

“With either option, you’re gambling—and when you’re talking about cancer, ‘gambling’ is an ugly word,” he says. “Overtreatment and undertreatment are very prevalent, and our goal is to get out of this cycle so we can improve the patient’s quality of life.”

The death rate from prostate cancer is going down and the disease is being discovered earlier, providing increased opportunity to use focal-laser therapy. Barqawi has successfully treated five prostate cancer patients since he began using the therapy in December 2009.

Patients have been able to leave the hospital the same day they arrive, without side effects, drugs or catheters. Along with eliminating complications, focal-laser therapy costs less than the more common approaches to treating the disease.

Before hitting the cancer with a laser, Barqawi uses 3-D mapping to pinpoint it. (He and the application were featured in a Wall Street Journal article March 31, 2009.) “If I want you to arrest someone in the town where you live, but I don’t give you the address, you have to arrest the whole town. So 3D mapping, like MapQuest, makes so much sense,” he says. Barqawi has performed hundreds of biopsies using this minimally invasive approach.

The ideal candidate for focal-laser therapy, which surgeons at Duke, Harvard and Stanford are now following, is a patient like Duke Altschuler (see page 9). Altschuler fit the common profile: His prostate specific antigen, or PSA, was elevated and he underwent a biopsy, indicating a very small area of the cancer.

Although Barqawi sounds like a man whose entire medical career has focused on managing or eradicating prostate cancer, he hasn’t always been a urologist. A former breast cancer surgeon, he saw opportunities to vastly improve the treatment and management of this most commonly diagnosed disease in men, to catch up with progress being made in the diagnosis and treatment other cancers.

One thing hasn’t changed, though: For clinical care providers such as Dr. Al Barqawi, it all comes down to this: “How can we do better for our patients? Here at the Cancer Center, we are solving problems.”

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Al Barqawi, MD, FRCS Specialty: Prostate cancer, minimally invasive surgery Research interests: New minimally invasive diagnostic and treatment interventions for prostate cancer

CLINICAL CARE

Duke Altschuler Diagnosis: Prostate Cancer Physician: Dr. Al Barqawi

By Mary Lemma

Focused “Zapping” Is the Right Fix for This Engineer When in November 2009 a surgeon asked Duke Altschuler if he was planning to have any more kids, the Denver engineer and businessman paused. “That kind of wakes you up,” he recalls.

But for Altschuler, 58, who with his wife Melisse Perré owns a Denver garage, it wasn’t a question of having kids. (They have four.)

It was a question of quality of life and what else could be done to reasonably ensure it without the side effects typically associated with invasive prostate cancer treatment.

Altschuler’s prostate specific antigen (PSA), which he and his physician had been monitoring for years, had begun fluctuating, a sign that alerted Altschuler to a problem.

His father died of prostate cancer at 60.

His wife began researching the options for treatment and learned that a family friend had been a patient of Dr. Al Barqawi, a University of Colorado urologist and surgeon internationally renowned for using 3-D mapping to precisely locate prostate cancer and target it for treatment. Barqawi had successfully treated prostate cancer with cryogenic therapy, but for Altschuler—an early-stage patient—the surgeon suggested something with even more potential: focallaser therapy, in which the cancer is “fried,” not frozen. Focal-laser treatment uses a proton beam to target the cancer with even more precision than cryogenic therapy.

“It wasn’t difficult to understand,” he recalls.

“I’m an engineer and a German, so it doesn’t take long to get from A to B. Dr. Barqawi really put it in layman’s terms.” Although Barqawi insisted his patient go home and think about it, by the time Altschuler got to the parking lot, “I’d made up my mind and called him right then.” He didn’t like the other options—watchful waiting or surgery— given his family history.

“Some prostate cancer surgery is like taking a sledgehammer to hit a tack,” he says.

“The cryogenic approach is like a smaller ball peen hammer, so you’re getting closer.

But the focal-laser treatment is like using your thumb on that tack.”

Altschuler was treated at University of Colorado Hospital in May 2010 and went home the same day. (He recalls: “I felt as though I could get on a plane.”) There has been no recurrence, and from now on, he’ll be monitored with blood tests. Until his PSA increases, he says, that’s all that needs to be done.

Since his treatment, Altschuler has worked full time running Duke’s Garage, collecting and restoring classic old cars and converting many of them to green, an idea for which he gives his wife credit. He also is a founder of a company that distributes steel casings for the oil-drilling industry.

“The university was really impressive.

Everyone knew what they were doing, and everything Dr. Barqawi said he was going to do, he did.”

Altschuler is no stranger to considering all manner of approaches to illness. “I’ve met all kinds of people, even shamans [when one of his children was ill], so I’ve seen some real out-of-the-box stuff,” he says.

“Dr. Barqawi was thinking outside the box, and being scientific and logical.”

He is grateful, too, for his doctor’s sense of humor and “humble” bedside manner. “I’m really high on Dr. Barqawi . That man’s a real healer.”

Please Support UCCC: www.uccc.info/give.

“When you turn 50, things are worth checking,” Altschuler says. “ It’s like taking your car in for maintenance. When you hit 50,000 miles, it’s time for a check-up.

Nobody wants to hear ‘the big C’; that’s bad news. But the good news with this is, ‘you’ll live.’”

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COMMUNITY

Mary Lee and Don Beauregard Areas Supported: General Cancer Research and Care

By Lynn Clark

“It’s the only place we’d go.”

Mary Lee Beauregard hates cancer. Breast cancer took her mother at the age of 47, and throat cancer took her father at the age of 80. One of her aunts has had cancer.

Her husband, Don, has a photo of six of his dearest friends at a wedding 10 years ago. Since then two died of cancer and two discovered cancer. “I have it on my desk, and it’s just pretty indicative of some of the impact we’ve seen from cancer with frien ds and family,” he says.

Mary Lee says, “There’s nothing we’d like to see more than better treatments, fewer people being affected, and of course, a cure.”

Their commitment to funding cancer research began 30 years ago, when a serendipitous meeting with pioneering radiologist William Jobe, MD, led them to create the Nancy Gosselin Foundation.

“Dr. Jobe’s desire to find a platform outside his practice to raise money and awareness for cutting-edge breast cancer treatment in the late 1970s created a synergy with our desire to memorialize Mary Lee’s mother,” Don says. “The foundation had a modest beginning, but it really evolved into something special, thanks to our collaboration with Dr. Jobe.

He was always reaching for the stars and brought some of us along.”

The foundation eventually became part of what is now the AMC Cancer Fund, one of the University of Colorado Cancer Center’s fundraising partners. Since then the Beauregards have been active participants in CancerCure, an annual giving organization benefiting UCCC, and Mary Lee has served

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on the UCCC board and chaired the CU Foundation board.

In the 1990s, Mary Lee took a job at the University of Colorado, first as director of public affairs, then as special assistant to the chancellor of the university’s health sciences campus.

“Through my involvement, it was clear to me how good our cancer center was,” she says, clearly so committed to the cause as to speak in the collective. “We have been able to draw incredible faculty to our program because of [UCCC founder] Dr. Paul Bunn and Dr. Bill Robinson. And now to get Dr. [Dan] Theodorescu as our second director to follow Paul—that says a lot. Paul is a star, and it seems like Dr. T is going to be a star also.”

As special assistant to the chancellor, Mary Lee was present at a pivotal meeting where the deal was struck to transfer the former Fitzsimons Army Hospital base to the University.

“It was Paul Bunn, Sen. Ted Stevens, who was head of the appropriations committee at the time, Sen. Ben Nighthorse Campbell, the chancellor and me at a table at the Brown Palace at 7 am on a Sunday,” she recalls. “We needed an $8 million appropriation, and we got it. I’ll never forget sitting there, and Ted Stevens making that commitment.”

The first funding went to building the Anschutz Outpatient and Cancer Pavilions on what is now the Anschutz Medical Campus.

Initial projections showed the campus would be built out in 50 years, Mary Lee recalls.

“And then it was 20 years, and thanks to the Anschutz family and other generous families

like the Leprinos and the Grohnes, it was built out in eight years,” she says, grinning.

“That was incredible. And we’re out of space, and both hospitals [University of Colorado Hospital and The Children’s Hospital] are expanding!”

The Beauregards say their continued commitment to both giving money and raising money for the Cancer Center is easy to make.

“We support it because it’s the best,” Don says. “It’s a critical time. They are making tremendous strides, they have great leadership.

This is the time when donors are getting the biggest bang for their buck. So many things have come together, and it’s like wow, now let’s propel it, let’s take it to the next level.

But in order to do that it’s going to take people really reaching down deep and supporting it.”

Mary Lee says, besides raising money for the Cancer Center, she’s doing her best to make as many people aware of its excellence as she can.

“There is no need to leave Colorado,” she says. “We have an amazing cancer center.

You could go story after story of people who had cancer here and they would say that’s absolutely right—the care is amazing, they have the latest technology, and the facility is wonderful. And it’s wonderful because of the people who have given, who made—for an awful situation—a wonderful place for people to go to get outstanding care.

“It’s the only place we’d go.”

Please Support UCCC: www.uccc.info/give.

COMMUNITY NEWS

AMC Cancer Fund, Golfers Against Cancer donate $200,000 for seed grants AMC Cancer Fund and Golfers Against Cancer have given four groups of UCCC researchers seed grants to investigate new solutions to cancer.

Golfers Against Cancer, a nonprofit in its second year of raising money for UCCC through a golf tournament and auction, presented UCCC Deputy Director Andrew Thorburn, PhD, with a check for $70,000 in October. The group’s board selected two projects to fund with $35,000 each: • Aik-Choon Tan, PhD, James DeGregori, PhD, and Chris Porter, MD: Implementation and refinement of high throughput functional genomic screening • Rui Zhao, PhD, and Qinghong Zhao, PhD: Targeting a Transcriptional Co-repressor CtBP for Cancer Therapy.

“We’re taking an investment banker approach by helping to select projects with the best chance to get additional funding,” says Scott Pearson, Golfers Against Cancer’s president. “We know from giving to UCCC researchers last year that seed funding can lead to bigger grants and new treatments.”

In 2009, the group’s donation helped fund a gastrointestinal cancer tissue bank that resulted

Cocktails for a Cure Feb. 3

in a $1 million National Cancer Institute grant to UCCC member Wells Messersmith, MD. AMC Cancer Fund, one of UCCC’s fundraising partners, stepped in with additional funding to bring both 2010-funded projects to $50,000. AMC also funded two additional projects:

potential, but have no other source of funding. It’s very rewarding to us and our donors and volunteers to think that we could help get the ball rolling on an idea that could, just a few years from now, really make a difference to people with cancer.”

• Xuedong Liu, PhD, and Dan Chan, PhD: Effective Treatment of Human Tumors with Isoform-specific Histone Deacetylase Inhibitors ($50,000) • Allen Waziri, MD, and Don Bellgrau, PhD: Oral Arginine Supplementation for Improving Global Cellular Immune Function and Efficacy of Whole Yeast-based Vaccination in Glioblastoma ($20,000, additional $30,000 in funding from an unnamed donor and UCCC)

Grantees Bellgrau, Porter, Chan, Liu, DeGregori and Zhao

AMC Cancer Fund CEO Alice Norton says kickstarting interesting and promising research is among AMC’s goals.

“It’s clear that every dollar invested in seed grant funding yields many more dollars from federal and private agencies, providing a great return on investment,” she says. “These projects were chosen because they are collaborative and show great

UCCC deputy director Dr. Andrew Thorburn and Scott Pearson

Anschutz Foundation gives $1 million to UCH cancer expansion Community leaders and University of Colorado Hospital faculty and administrators broke ground on the hospital’s cancer center expansion on Oct. 4, bolstered by a $1 million gift from the Anschutz Foundation.

“I hope this will encourage others to give,” said Christian Anschutz, son of businessman and philanthropist Phillip Anschutz, for whose family the facility is named.

AMC Cancer Fund presents Cocktails for a Cure on Feb. 3, 2011, at Lowry’s Soiled Dove Underground to support the UCCC Young Women’s Breast Cancer Translational Research Program. Imbibe, nosh, mingle and be entertained at the 2nd Annual Women’s Event. Bring a girlfriend and sip on a signature cocktail created by guest bartenders from some of Denver’s top establishments while enjoying an lively celebration of Colorado women. This year’s honorary chairs include Sue Allon, Keri Christiansen, Laura Dear and Bertha Lynn. Tickets are $150 and available at www.amc.org/events.

Expansion campaign chairman Steve Bangert said the campaign had raised $10 million toward a $20 million goal. The expansion will add more than 40,000 square feet to the cancer pavilion and includes the renovation of another 11,200 square feet. The expansion will add more room for clinical care, more physicians and add clinical research capacity.

CSU Animal Cancer Center receives $3 million gift for endowed chair The Flint Animal Cancer Center at Colorado State University, a UCCC consortium member, received a $3 million gift from the Shipley Foundation to create the Shipley University Chair in Comparative Oncology.

The university chair, which will be filled via an international search, helps support translational research between animal and human cancer treatments and cancer prevention.

“This gift is a culmination of 10 years of friendship between the Shipley family and the Animal Cancer Center, as well as the Shipley family’s commitment to finding creative and groundbreaking tools to beat cancer,” said center director Rod Page, DVM. “Three generations of the Shipley family have shared and supported our vision that understanding the connections between cancer in people and cancer in pets helps all species.”

The center is the largest of its kind in the world, treating about 1,500 pets annually from around the globe and comparing information and research results with many human cancer programs, including UCCC. www.uccc.info/c3 | C3: FALL 2010 | 11

FALL 2010 w w w.uccc.info/c3

C3: Collaborating to Conquer Cancer Published three times 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.)

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Editor: Lynn G. Clark 303-724-3160, Lynn.Clark@ucdenver.edu Contributing Writers: Mary Lemma, Michele Conklin and Erika Matich Photos: Lynn Clark and Glenn Asakawa, CU Photography Design: Ebb+Flow Design The University of Colorado Cancer Center is Colorado’s only National Cancer Institute-designated comprehensive cancer center. Headquartered on the University of Colorado Denver Anschutz Medical Campus in Aurora, UCCC is a consortium of three universities and five institutions that are dedicated to cancer care, research, education and prevention and control.

UCCC Consortium Members Universities Colorado State University University of Colorado at Boulder University of Colorado Denver Institutions University of Colorado Hospital The Children’s Hospital National Jewish Health Denver Health Medical Center Denver Veterans Affairs Medical Center Visit us on the web: www.uccc.info UCCC is dedicated to equal opportunity and access in all aspects of employment and patient care.

The Message: Andrew Thorburn, PhD, UCCC Deputy Director

Seed Grants Plant a Forest One Tree at a Time this $200,000 investment may seem insignificant.

But it is incredibly significant, and here’s why.

Thorburn with Golfers Against Cancer board members and grantees

On October 29, Denver Golfers Against Cancer [GAC] gave the University of Colorado Cancer Center a check for $70,000, which they’d raised at August’s golf tournament, dinner and auction.

The GAC board didn’t want to just give us money.

They wanted to give us money to make an immediate, measurable impact. So, we created an opportunity for UCCC members to apply for small grants, which were reviewed by a panel of their peers. The best five were forwarded to the GAC board, who chose two projects to receive $35,000 each.

AMC Cancer Fund, a UCCC fundraising partner, contributed $100,000 to bring the GAC grants to $50,000 each and support the three other projects.

[You can read more on page 11.]

UCCC scientists receive a collective $140 million a year in grant funding. In the scheme of things,

Cancer research funding is a highly competitive business. Researchers across the country submit grants to the National Cancer Institute and other federal institutions, and only the top 10-15 percent will be funded. To get a fundable score, applicants need three things: 1. A good idea … but ideas are cheap.

2. A track record that shows you—and the institution you work for—have been successful in the past.

3. Evidence that your idea will work.

Seed grants, like those funded by GAC and AMC Cancer Fund, give our scientists time to come together, to show they can work together and that they are worthy of a top 10 percent score.

Seed grant funding is what gets the ball rolling.

Without it, no scientist could investigate a new idea, or bring together people on a project for the first time, because most other funding sources require proof that your idea—and your team—will work before they are fundable.

Here’s an example: About four years ago, Drs. Mark Gregory and James DeGregori received a $30,000 grant from Cancer League of Colorado, another of our stalwart seed grant funders. Using that money, they discovered a new, druggable pathway

in leukemia. Within a year, they converted the $30,000 into a $540,000 grant from the Leukemia & Lymphoma Society to further the work. And in the near future, that work will be in a clinical trial for children with leukemia, run by Dr. Chris Porter, another UCCC member.

Here’s another: Dr. Wells Messersmith received a $1 million grant from the National Cancer Institute this summer because he and colleagues developed a new tissue bank using GAC donations last year—a 30-fold increase in the initial $30,000 investment. The resource is already leading to new discoveries that will directly help patients with colorectal cancer in the near future.

Even more amazing: The grants from GAC and AMC Cancer Fund came because individual people donated $25, or $100 or even $1,000. Their money was pooled to make the grants, and those grants may be leveraged for millions of dollars from federal and private sources to make a real impact on individual patients down the line. In other words, there is no such thing as a small donation.

That’s the power of seed grants in cancer research: They turn single trees into forests.

Please Support UCCC: www.uccc.info/give.