C3: Collaborating to Conquer Cancer Fall 2012
The University of Colorado Cancer Center's fall 2012 edition of C3: Collaborating to Conquer Cancer Magazine.
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 W I N T E R 2 012 TIGHTENING THE BODY’S CANCERCATCHING NET 12: OUTLIVING THE ODDS 16: TOBACCO TAX SAVES LIVES 10: Q&A WITH SONIA OKUYAMA, MD 11: C3 MD CLAYTON SMITH 18: SUPPORTER FOCUS ON CANCERCURE ANSCHUTZ MEDICAL CAMPUS N3WS CU CANCER CENTER RECEIVES PRESTIGIOUS DESIGNATION N E W C L I N I CA L T R I A L D E S I G N P R O M I S E S TO AC C E L E R AT E CA N C E R D R U G A P P R OVA L S The University of Colorado Cancer Center remains in distinguished company, having earned a prestigious designation from the National Cancer Institute (NCI). This is the fourth time CU Cancer Center has been named a comprehensive cancer center by the NCI—one of only 41 cancer centers in the U.S. to receive Patients with early-stage breast the designation. cancer usually have to wait years “This designation means we are among the ‘best of the best’,” says Dan Theodorescu, MD, PhD, director of CU Cancer Center. “We are proud to bring that level of care to our community, while to receive new cancer drugs, continuing to research and develop clinical trials that keep our patients living longer.” but new guidance from the FDA promises to substantially reduce The Cancer Center is also one of only a handful of comprehensive cancer centers that have the “consortium” designation, meaning the center includes members from multiple universities: the time and cost of getting University of Colorado Denver, University of Colorado-Boulder and Colorado State University. new treatments to patients. The approach is based on a trial University of Colorado Health System (including University of Colorado Hospital, Poudre Valley Hospital, Medical Center of the Rockies and Memorial Hospital), Children’s Hospital Colorado, Denver design being tested in the I-SPY Health, Denver VA Medical Center, National Jewish Health and Kaiser Permanente Colorado are the 2 TRIAL, an innovative phase II consortium patient care partners. breast cancer trial at CU Cancer Center. ELI AS “New cancer drugs are usually tested first in CU Cancer Center is the only NCI-designated comprehensive cancer center in Colorado. This recognition comes on the heels of the U.S. News and World Report rankings placing CU Cancer Center patients with advanced stage disease and then among the top 35 cancer centers in the U.S. The NCI re-designation lasts for five years and provides a approved for use in early-stage cancer but only budget of approximately $18 million over that period. after additional clinical trials. It can take hundreds of thousands of dollars and several years to study one drug,” says Anthony Elias, MD, breast cancer program director at CU Cancer Center. “I-SPY MISIDENTIFIED AND CONTAMINATED CELL LINES LEAD TO FAULTY CANCER SCIENCE CASEY CASS Modern cancer therapies start in cells: Researchers compare cancer samples to healthy cells to discover how cancer is 2 shows us that we can find the treatments that work and get them to patients who need them efficiently and safely.” The new FDA recommendations, discussed genetically different and use cell lines to test in The New England Journal of Medicine, would promising new drugs. However, a CU Cancer speed up approval of drugs tested prior to surgi- Center study shows that due to a high rate of cal removal of tumors in certain types of high-risk contamination and misidentification in widely patients with localized, early stage disease. available cell lines, researchers may be draw- The I-SPY 2 Trial uses specific genetic signa- ing faulty conclusions. tures—biomarkers—in patients’ tumors to select “I’ve seen faculty and graduate students those most likely to benefit from testing using leave my lab in tears when we discovered the the new approaches. The biomarkers are also cells on the label weren’t the cells they were actually experimenting on,” says Christopher Korch, PhD, CU Cancer Center investigator. “When you get a cell line, you have to look that gift horse in the mouth—there’s up to a 40 percent chance it’s a Trojan horse, not what it says it is.” While a misidentified cell line seems likely due to a snafu on the part of a lab assistant with a faulty filing system, there are more ways than clerical error to end up with the wrong label on a sample of cells. “I see two people working with different cultures in the same hood, or using the same growth medium for the same cultures with the same pipette,” Korch says. In order to keep results from being flawed, Korch and others are putting their data online and allowing investigators elsewhere to compare their cell lines to the group’s controls. They recommend researchers check their cells prior to bringing them into the lab or put them in quarantine until they know what they are. incorporated into a unique “adaptive” trial design that allows researchers to measure the relative benefit of treating patients with different tumor profiles with a specific drug, and guide treatment assignments for subsequent trial participants. I-SPY 2 can test new treatments with significantly fewer participants and in half the traditional time, which will dramatically lower costs. The trial, launched two years ago, is screening multiple cancer drugs at 19 major cancer research centers across the country, including CU Cancer Center. BLADDER CANCER PATIENTS MAY BENEFIT FROM ANTI-ANDROGEN THERAPY Bladder cancer patients whose tumors express development and spread to other organs depends aggressive bladder tumors, but that CD24 in fact high levels of the protein CD24 have worse significantly on CD24, which in turn depends on drives the aggressiveness of these tumors. prognoses than patients with lower CD24. CU androgens like testosterone,” Theodorescu says. Cancer Center Director Dan Theodorescu, MD, “By taking away these androgens, we may be able the rationale for clinical studies of anti-androgen PhD, shows that CD24 expression may depend on to greatly diminish the proliferative and metastatic therapies with bladder cancer, especially in those androgens—and that anti-androgen therapies like power of bladder cancer cells.” tumors that happen to test markedly high in CD24 those currently used to treat prostate cancer may benefit bladder cancer patients. “This is a major finding. Bladder cancer 2 WWW.COLORADOCANCERCENTER.ORG Working with mouse models and human tumor “We hope the results of these studies show expression,” Theodorescu says. “The next step is samples, Theodorescu and colleagues showed moving this promising therapy to clinical trials with that not only do high levels of CD24 mark more human patients.” 90 % MILK THISTLE HITS PROSTATE CANCER TWO WAYS FLIC KR C RE AT IVE C OMMONS Tumors are gluttons. In order to fuel their A B N O R M A L LY L O W L E V E L S O F G R OW T H HORMONE astounding growth rate, they must gorge. A CU Cancer Center study pinpoints the compounds derived from milk thistle that best kill cancer cells directly and restrict tumors’ ability to grow the new STUDY SHOWS LONG-TERM EFFECTS blood vessels they need to import this massive OF RADIATION IN PEDIATRIC food supply. CANCER PATIENTS C ASE Y C ASS In his study, Gagan Deep, PhD, CU Cancer Center investigator and research assistant professor in the Skaggs School of Pharmacy and Pharmaceutical Sciences, found that mice that were orally fed Isosilybin B at 50 or 100 mg/kg body weight had much lower tumor volumes than untreated mice and significantly lower tumor volumes than mice treated with the other three isoforms of silibinin. This Isosilybin B most effectively killed cancer cells directly. For many pediatric cancer patients, total body But directly targeting cancer cells isn’t the only M I L K TH I S TL E irradiation (TBI) is a necessary part of treatment way to restrict tumor growth. Also important is a during bone marrow transplant and a key to tumor’s ability to grow new blood vessels that import food. The body lines blood vessels with endothe- long-term survival. But lengthened survival lial cells, and “while Isosilybin B was most effective towards prostate cancer cells, it was least effective creates the ability to notice long-term effects towards endothelial cells,” Deep says. “On the other hand, Silybin A showed highest efficacy towards of radiation as young cancer patients age. endothelial cells.” A CU Cancer Center study details these late effects of radiation. “These kids basically lie on a table and truly do get radiation from head to toe. There is a Gagan’s group plans to test a mixture of these two strongest isoforms: Silybin A and Isosilybin B. They anticipate B will target the tumor and A will target its ability to grow new blood vessels. “We hope to find a synergistic effect between these two promising compounds,” Deep says. Tomorrow’s drugs may come from the plant that today grows on the side of the road. little blocking of the lungs, but nothing of, for example, the brain or the kidneys,” says Jean Mulcahy-Levy, MD, research fellow at DIETARY SUPPLEMENTS INCREASE CANCER RISK CU Cancer Center and the paper’s first author. Beta-carotene, selenium and folic acid—taken up to three times their recom- Of 15 patients who received TBI before age mended daily allowance, they’re probably harmless. But taken at much higher 3, many developed endocrine and metabolic levels, as some supplement manufacturers suggest, they can increase the risk problems including testicular malfunction, of developing a host of cancers. restrictive pulmonary disease due to high “It’s not that these nutrients are toxic,” says Tim Byers, MD, MPH, professor levels of blood triglycerides, and cataracts. of epidemiology at the Colorado School of Public Health and associate director Likewise, 90 percent of patients showed abnormally low levels of growth hormone and for prevention and control at CU Cancer Center. “They’re essential and we need them, but we need them in a certain balance.” BYERS 71 percent were considerably under height. Currently the FDA regulates dietary supplements as food, but, as Byers Additional late effects of TBI included kidney, and colleagues suggest, supplements, especially at high doses, are more liver, skeletal and cardiac malfunction, and accurately described as inhabiting a mid-ground between food and drugs. cognitive decline. Like drugs, supplement ingredients are biologically active—sometimes for “Fifteen doesn’t seem like a large number, better and sometimes for worse. but because we have such a good pediatric “We need to do a better job as a society in ensuring that the messages bone marrow transplant program at Children’s people get about value versus risk is accurate for nutritional supplements,” Hospital Colorado and a radiation therapy Byers says. “My conclusion is that taking high doses of any particular nutrient program at CU Cancer Center, we were able is more likely to be a bad thing than a good thing.” to get a large enough cohort of patients to see these overall effects,” Mulcahy-Levy says. “It’s not so much that you want to stop TBI, which is frequently a necessary part of treatment, but this study shows it’s important to know about these problems in order to address them appropriately and proactively,” she says. Get more CU Cancer Center news on our blog: www.coloradocancerblogs.org Sign up for our bimonthly newsletter, Colorado Cancer News. Scan to subscribe. 3 C3: WINTER 2012 TIGHTENING THE BODY’S At CU Cancer Center, researchers discover how dinosaurs, diabetes, Star Trek extras and Keith Richards combine to keep the body cancer-free. 4 WWW.COLORADOCANCERCENTER.ORG I nterstate 70 is bad enough on a normal Monday evening, let alone when an accident makes the freeway look more like long-term parking at Denver International Airport. And so it’s easy to sit there, stewing, scanning radio stations, and thinking about what could possibly have caused the accident in front of you and why the highway patrol can’t move the wreck to the median. I mean—sheesh—you could be home by now sitting comfortably on the couch and grumbling about Peyton Manning’s arm! That is, if it weren’t for that darn accident. But look at it another way: most nights the freeway is packed with 4,000-pound chunks of fire-propelled metal, hurtling across the pavement at 70 mph while their pilots shove their heads in Cheetos bags or fidget with their supposedly hands-free smart phone systems. Some of these people you wouldn’t trust with a popcorn maker let alone a Hummer. Really, it’s pretty astounding there aren’t more accidents. The same is true of cancer. Cancer research centers tend to focus on what to do once the body is sick, once an accident is already on the road. For example, at University of Colorado Cancer Center when a patient walks in the door the physician asks what went wrong and how to fix it. “But maybe a better question is, for all the people we don’t see, what goes right,” says Andrew Thorburn, PhD, deputy director of CU Cancer Center. He points out that there are about 10 to 100 trillion cells in the human body, with 50 to 60 billion cells replaced every day. That’s 50 to 60 billion chances per day that a cell can accidentally accumulate a mutation or combination of mutations that cause cancer. Like cars on a fast freeway, “You look at those odds and it’s surprising that cancer isn’t more prevalent,” Thorburn says. Or maybe it’s not that surprising after all. FLI CKR/MIEMO CC LICENSE CANCERCATCHING NET VE E R GLE NN ASAKAWA BY GARTH SUNDEM Andrew Thorburn, PhD, with professional research assistant Josh Thompson and postdoctoral researcher Paola Maycotte. It’s no random accident—no game of Russian roulette—that keeps the body cancer free. Instead it’s a handful of precise mechanisms that Thorburn calls “prerequisites of multi cellular life” that have evolved to ensure we stay healthy long enough to pass on our genes. Researchers at CU Cancer Center and elsewhere are broadening their focus to explore not only what goes wrong when we get cancer, but what goes right when we don’t. “MAYBE A BETTER QUESTION IS, FOR ALL P LAC E O R I G I NAL FAC E D OWN O N G LAS S MORE PREVALENT.” First, “the body has an astoundingly precise copy machine,” Thorburn says. When a cell divides, it copies the full expanse of its DNA, giving away a copy to its daughter cell and keeping a copy for itself. The code of life is made up of only four bits of information, called nucleotides, which when strung together can look something like this: ATGACGGAGCTTCGG. If you were sitting at a keyboard, could you look at this code and reproduce it? What would be your error rate? The body’s error rate is only about one mistake in every 100,000 nucleotides. That’s pretty darn good. (See “Decoding Cancer,” page 9.) Now imagine the 30,000-ish genes included in every human cell’s DNA—the blueprints for all the construction and workings of your body. Each gene is made up of about 3,000 nucleotide base pairs. That’s not all: functional genes make up only about 2 percent of your DNA and so in all you have around 6 billion nucleotide base pairs in each cell’s DNA. This means that despite the body’s careful copy machine, each new cell is likely to have about 120,000 mutations. Now multiply that by 50 to 60 billion cells and you get…well, you get a really big number that you certainly don’t want to see printed here. —ANDREW THORBURN, PHD THE PEOPLE WE DON’T SEE, WHAT GOES RIGHT? YOU LOOK AT THOSE ODDS AND IT’S SURPRISING THAT CANCER ISN’T 5 C3: WINTER 2012 VE E R So in addition to an accurate copy machine, the body also has an accurate proofreader. Instead of accepting these mutations, the body tries to identify and fix them. A cell builds DNA by stacking it one nucleotide at a time. And as it stacks nucleotides, the cell has enzymes that crawl along the original DNA, comparing it to the copy. When an enzyme finds an error—say a G that should be an A—it pulls the mistake and inserts a correction. The cell’s proofreading mechanism catches and fixes about 99 percent of errors this way—good but not nearly good enough to keep mutations out of your genome. The more cells you need to replace (for example, because you kill cells with a sunburn), and the higher a cell’s mutation rate (say, because the sun’s UV rays slice and dice DNA like Dan Aykroyd’s Super Bassomatic on “Saturday Night Live”), the more mutations make their way past the copy machine and proofreader. Now the body’s job switches from fixing errors to eliminating them. LYNN CLARK C O PY C O R R E CTLY O R K I LL Jill Slansky, PhD, co-leader of the Immunology and Immunotherapy Program at CU Cancer Center and National Jewish Health. 6 WWW.COLORADOCANCERCENTER.ORG As you’d expect, one recognizer-and-killer is the immune system. But it’s tricky: cancer cells are your own cells gone bad. Your immune system is supposed to kill foreign cells like bacteria and viruses, not your own cells, and so it has difficulty turning its firepower on more domestic terrorists. Interestingly, there’s one kind of person whose immune system does kill cancer cells and that’s people with autoimmune diseases like Type 1 diabetes, in which the immune system’s T-cells erroneously attack the pancreas’s insulin-producing cells. Patients with Type 1 diabetes almost never get pancreatic cancer. And patients with the autoimmune condition vitiligo, in which T-cells attack the skin’s pigment-producing cells, are dramatically protected against skin cancer. It seems that an over-sensitive immune system kills cancer cells first. On the flip side, people who are immunocompromised, as are those with HIV, have higher rates of many cancers. “When you develop a cancer, by definition soft tissue has gone haywire. And when you develop an autoimmune condition like Type 1 diabetes, by definition your T-cells have gone haywire,” says David Wagner, PhD, CU Cancer Center investigator and associate professor of medicine at the CU School of Medicine. “Perhaps we could push T-cells to just beneath this threshold of ‘haywire’ to combat the cancer cells that have already gone past this tipping point.” It’s like your email spam filter: one form of cancer immunology seeks to dial up the sensitivity of your immune system’s spam filter in order to route cancer cells to the “kill” folder, perhaps destroying some healthy cells along the way. Wagner is working to control T-cell sensitivity with a protein called CD40. Tweaking CD40 in one direction makes T-cells more aggressive and tweaking it in another direction makes T-cells more docile. Other CU Cancer Center immunologists are working with vaccines to sensitize T-cells against cancer. According to Jill Slansky, PhD, co-leader of the Immunology and Immunotherapy Program at CU Cancer Center and National Jewish Health, here’s one way it works: “The immune system is designed to recognize abnormal proteins and kill the cells that present these proteins. Due to mutations, cancer cells make abnormal proteins, but because cancer cells also share so much similarity with the body’s own, healthy cells, the immune response may not be very strong. “We’re working to boost the sensitivity of T-cells to these tumor-specific antigens. Like any vaccine, if you can give T-cells a preview of these foreign proteins, you can sensitize T-cells to recognizing these proteins on actual cells,” Slansky says. SAC R I F I C I N G C E LLS F O R TH E G R EATE R G O O D GLENN ASAKAWA VE E R In fact, cells containing cancer-causing mutations might not even need the intervention of the immune system to end up dead. “Cells are hardwired to kill themselves if there’s something wrong with them,” says Thorburn, whose research focuses on this programmed cell suicide called apoptosis. “If a cell’s in the wrong place or growing at the wrong time, healthy cells have this natural default to just kill themselves.” Like an unnamed character tagging along with the “Star Trek” crew on an unexplored planet, cells are expendable. So the body errs on the side of caution—one teeny-tiny false move in the way a cell goes about its business can show that it harbors a dangerous mutation, and the body would rather throw the cell under the bus than risk it spawning a dangerous tumor. For example, if you’ve taken high school biology, you probably still have that dream where you’re sitting at a desk, pencil in hand, no clothes, staring at an unexpected test on the stages of the cell cycle. Messing up the steps of the cell cycle won’t help your biology grade and it doesn’t help most cancer cells, either. That’s because the body places customs agents at the boundary of each step. If a cell rushes through or tries to skip a stage of cell division, tumor suppressor genes (customs agents) recognize the cell and mark it for apoptosis. Likewise, these regulators look for broken DNA, unnatural bulging or misarranged chromosomes—any one of these can mark a cancerous cell and any one can get a cell marked for apoptosis. So in addition to a mutation that allows an early cancer cell to act cancerous, cancer cells also include mutations to these anti-tumor or tumor suppressor genes, making them toothless. In fact, “Simply disabling some of those anti-cancer genes is sufficient to create cancer,” says Thorburn, “and ironically, cancer cells are often easier to push into apoptosis than healthy cells—it’s as if they were trying to kill themselves and just didn’t quite manage it.” D I N O SAU R S , K E I TH R I C H AR D S AN D TH E B O DY’ S C H A N G I N G T I S SU E LAN D S CAP E Then in addition to accurate copying, the immune system and apoptosis, there’s the role of the tissue surrounding mutated cells. Sure, the older you are, the higher likelihood that one of your 50 to 60 billion cell duplications per day will result in a sneaky mutation that avoids control, but Cancer Center researcher James DeGregori, PhD, shows that it’s not only the increasing chance of a mutation with time that leads to higher cancer rates in older adults. “You put an early cancer cell in healthy tissue and that cancer cell is unlikely to survive,” says DeGregori, professor of molecular biology at the CU School of Medicine. “It’s like what happened to the dinosaurs 65 million years ago. Dinosaurs were great and they weren’t changing that fast; they were well adapted to their landscape. Until that darn meteor. Suddenly dinosaurs weren’t a good fit for the new landscape. The species didn’t have to change their mutation rate; it was the new landscape that drove speciation. “Similarly, what primarily drives cancer rates higher as we age is the changed landscape,” he says. Our healthy cells are optimized for the conditions of our healthy, younger tissue. In fact, they’re so perfectly optimized for young tissue that changing anything about a cell makes it less fit for its surroundings. That’s the case of cancer cells—they’re different James DeGregori, PhD (standing), with postdoctoral researcher Curtis Henry. 7 C3: WINTER 2012 VE E R and thus less fit, and so healthy cells simply out compete them. The young body uses basic survival-of-the-fittest to keep cancer in check. But, “when tissue is old, healthy cells are no longer a perfect fit for the landscape, and mutations might help a cancer cell adapt in ways a healthy cell can’t,” DeGregori says. Blot out the sun with a meteor’s cloud of dust and mammals will eventually outcompete thunder lizards. Age or transform tissue until it’s far enough from its healthy norm and cancer cells can outcompete their healthy peers. DeGregori’s work supports the conclusions of CU Cancer Center investigators Pepper Schedin, PhD, and Ginger Borges, MD, who work with the tissue landscapes that give rise to breast cancers. “We see that breasts with higher rates of inflammation—as those undergoing the process of involution during which milk-producing cells are replaced by fat cells—have higher rates of both initial cancer and metastasis,” Schedin says. Inflammation and a dramatically changing tissue landscape leave healthy cells looking for their footing, while cancer cells, like dandelions, take advantage of the disturbed earth. Borges and Schedin’s work explores the use of non-steroidal anti-inflammatory drugs like ibuprofen to reduce inflammation in these tissues, hopefully bringing it in line with the conditions for which healthy cells are optimized. OBESITY AND THE CHALLENGE OF PROVING PREVENTION “THE REAL DIFFICULTY IN EXPLORING ANY OF THESE PREVENTATIVE STRATEGIES IS THE LOGISTICAL AND ETHICAL DIFFICULTY OF PRESCRIBING ANY INTERVENTION FOR PEOPLE WHO AREN’T YET SICK.” —ANDREW THORBURN, PhD 8 WWW.COLORADOCANCERCENTER.ORG The influence of tissue on cancer is also important on a more global scale. The process of breast involution, sunburn and smoking are not the only ways to create inflammation. Obesity can also create cancer risk. (Read “Battle of the Bulge” in the previous edition of C3 at www.coloradocancerblogs.org for details.) In fact, Tim Byers, MD, MPH, professor of epidemiology at the Colorado School of Public Health and associate director for prevention and control at CU Cancer Center, believes that in many cases an intentional 10 percent weight loss after surgery for breast cancer can be as effective as adjuvant chemotherapy in preventing relapse. Knowing these mechanisms the body uses to stay cancer free, you’d think we could design and test interventions to help the body with its work and artificially boost its defenses. Unfortunately, “the real difficulty in exploring any of these preventative strategies is the logistical and ethical difficulty of prescribing any intervention for people who aren’t yet sick,” Thorburn says. For example, you can’t give 1,000 women ibuprofen and compare their breast cancer rates to 1,000 women given sugar pills. Likewise, you can’t experimentally introduce cancer proteins in a vaccine to people who don’t yet have the disease. Thus, prevention strategies are tricky to prove. But the times they are a-changing. Like CU Cancer Center, other cancer centers are starting to prioritize their departments of prevention and control. And cancer vaccines, including the drug Yervoy for metastatic melanoma and Gardasil for HPV that causes genitourinary cancers in men and women, have gone from fringe science to FDA approval. Next time you’re stuck in an I-70 traffic jam, instead of fretting in a way that’s really not good for your blood pressure, try being thankful that accidents are rare. In addition to being courageous as you face cancer, offering your compassion to others affected, and helping support organizations looking for tomorrow’s best fixes, take a minute to marvel at the body’s ability to get it right so often. We are machines made to resist cancer. By understanding how these machines work, we may find ways to help them resist cancer just a little bit better. DEC DINGCANCER HOW GOOD DNA GOES BAD A cell builds new DNA like zipping closed well to subsequent tines, and the difficulty attaching the next a winter coat, adding new zipper tines as the building blocks sounds an alarm that signals the DNA polymerase new DNA matches itself to the pattern DNA. But enzymes that do the actual stacking to quickly fix the problem. sometimes these two strands don’t stay perfectly zipped And then even after DNA replication is finished, the new strand together; sometimes they slip or wobble. is compared to the old strand and any mismatched bulges or other When the new strand slips, a little kink in the zipper can abnormalities are pruned and repaired. Any errors that remain after result in an extra nucleotide “tine.” When the pattern strand slips, stacking and checking are coded into the DNA as mutations, but even the kink can result in a missing nucleotide. then cells with abnormal DNA aren’t likely to survive to replicate. A wobble briefly makes a nucleotide “tine” on the pattern strand Cells have to pass frequent tests of normalcy—like a Tour de France able to grab a nucleotide tine other than its proper pairing—the rider taking a drug test at the end of every stage—and cells that rush wobble can insert the wrong nucleotide in the new strand. Most of through their lifecycle like a doping rider aren’t allowed to continue. these wobbles don’t last long—a mismatched tine doesn’t attach Doping cells are pruned by apoptosis—programmed cell suicide. NEW STRAND SLIP PATTERN STRAND PATTERN STRAND SLIP NEW STRAND PATTERN STRAND NEW STRAND MISMATCHED NUCLEOTIDE EXTRA NUCLEOTIDE MISSING NUCLEOTIDE 9 C3: WINTER 2012 A CONVERSATION WITH SONIA OKUYAMA, MD Assistant Professor, Medical Oncology, University of Colorado School of Medicine Director, Cancer Information and Counseling Line (CICL), CU Cancer Center BY GA RT H S U N D E M After medical school in Peru and an oncology fellowship at CU Denver, Sonia Okuyama, where survivors learn to manage and cope with MD, took a turn from the study of drugs and devices to the study of cures for the mind the increased distress that can be very poignant as well as the body. As the new director of the Cancer Center’s Cancer Information and in cancer survivors. The other component of this Counseling Line (CICL), Dr. Okuyama develops and implements interventions that help counseling program is to help patients adopt healthy patients cope with the many challenges of cancer outside the traditional conception of lifestyles—eating more fruit and vegetables and physical health. Here we talk with Dr. Okuyama about her work. exercising. As you can see, my research is about helping people through the cancer journey, not C3: How did you get interested in the I remember one patient in particular who was from the medical/drug standpoint, but from the psychosocial, whole-person standpoint. psychosocial aspects of cancer care? nearing the end of the medicines we could offer to Okuyama: Where I trained in Peru, we had none treat his colon cancer. We talked about palliative of the modern medicines or technologies. The care and end-of-life planning, but there was a wall C3: How do you think being trained as psychosocial aspect was fundamental to patient we couldn’t penetrate; he would shut us down. an oncologist and not necessarily as a care—many times it was all we had—so it’s close We were worried that without a proper discussion psychologist affects your work? to my heart. I see similar challenges during my he would end up dying in the ICU. Then he took Okuyama: We have phenomenal psychologists clinical work at Denver Health, where about half our part in the Dignity Therapy Project and it was such as part of our research team, but I do think it helps patients are uninsured. Even with insurance it can a breakthrough. Two or three months down the in many ways to have an oncologist bridge the gap be very difficult to get appropriate psychological road, when the time came, the transition to between these worlds to ensure a collaborative support, since coverage is so limited. My work is to end-of-life was completely opposite to what effort—and I’m happy to be such person. As any gather evidence that can help patients access this we feared. It was dignity. oncologist will tell you, every day we deal firsthand with highly distressed patients who seek not only integral part of cancer care. C3: And at other stages of cancer? the best medical treatments, but also a more holistic C3: So instead of treatments targeting Okuyama: We’re studying programs for cancer understanding of the cancer experience. Cancer cancer, what’s the focus of your research? survivors as well. For example, the C-STEPS care is definitely moving in that direction. I hope I can Okuyama: I have projects looking at the psycho- [Cancer Survivorship Telephone Education and help the University of Colorado Cancer Center offer social care of cancer patients at every stage of the Personal Support] program is a six-session tele- the most outstanding care, in the broadest definition disease. For example, the Dignity Therapy Project phone counseling program delivered by the CICL, of the word. G LEN N AS AKAWA is testing a structured videotaped interview as an intervention to improve psychosocial outcomes in advanced cancer patients. This allows patients to reflect back on their lives, what they want to leave behind and what they’re most proud of. Learn more about the free Cancer Information & Counseling Line at www.thecancerline.org or call 800-525-3777. The Cancer Information and Counseling Line helps patients cope with the many challenges of cancer. 10 WWW.COLORADOCANCERCENTER.ORG CLINICAL CARE GLE NN ASAKAWA MD Lured by Great Science, Collaboration N EW TO C O LO R AD O, C LAY TO N S M ITH I S ADVAN C I N G B LO O D CA N C E R TR EATM E NT AN D CAR E AT C U BY E R I K A MATI C H Great science is the main reason Clayton Smith Smith’s research involves manipulating ALDH came to Colorado. Easy access to beautiful genes to grow more normal stem cells, which in mountains, strong research collaborators and the turn compete against and eliminate leukemia stem opportunity to lead University of Colorado Cancer cells. Additionally, by learning to manipulate stem Center’s Bone Marrow Transplant Program are cells, he may help unlock the mystery of how additional perks. ALDH genes turn on cancer. “I visited Colorado over the years for scientific “If we can identify how blood stem cells ABOUT CLAYTON SMITH, MD Director, Bone Marrow Transplant Program, conferences and I loved it,” Smith says. “You’ve got become cancerous, the next step will be research- to love the mountains and the sunshine. Believe ing whether we can interrupt that process,” Smith University of Colorado Cancer Center me, after the gloomy, rainy weather in Vancouver, says. “Learning how these cells operate may also Professor of Medicine, University of Colorado B.C., the sunshine is a big deal.” help us identify existing targeted therapies or even School of Medicine Prior to coming to CU Cancer Center in develop new drugs to treat blood cancer.” One July 2012, Smith spent years fostering a long- day Smith, Vasiliou and other researchers could distance collaboration with a member of University discover how to prevent leukemia from developing of Colorado Skaggs School of Pharmacy and in the first place. Pharmaceutical Sciences faculty—Vasilis Vasiliou, Turning lab findings into targeted therapies PhD. For 25 years, Vasiliou’s laboratory has studied isn’t only a huge success for Smith and other aldehyde dehydrogenases (ALDHs) focusing on researchers; it’s also a success for patients around their role in metabolism, cellular responses to the world living with leukemia and a success for stress, metabolic diseases, cancer and cancer Smith’s patients at CU Cancer Center. stem cells. Smith and Vasiliou research the role of “When I was an intern at Parkland Hospital in ALDHs in controlling the growth of normal stem Dallas, Texas, one of my patients had acute leuke- cells and leukemia stem cells. mia and I could look under a microscope and see “Vasilis is the leading expert in the world on the his disease,” says Smith. “Patients like him have to ALDH gene family,” says Smith. “I read his papers, fight hard to beat leukemia and I want to find them followed his research, and then had the good hope and extend their lives.” fortune to meet him in San Francisco. We were Smith credits his enthusiasm to people— attending different conferences at the same time, to these patients and to his colleagues. “My but we sat down to a crab dinner and talked collaborators at CU Cancer Center are the most about science.” dedicated and passionate people in medicine,” Today, instead of multiple phone calls and Smith says—and he should know, having trained emails or meetings in other cities, Smith walks with leading experts from institutions including across campus. Memorial Sloan-Kettering Cancer Center, Moffitt “It is particularly nice on the University of Cancer Center, Duke University Medical Center and Colorado Anschutz Medical Campus to have a Stanford University Medical Center. That was before superb group of researchers all within easy walking becoming the director of the BC Cancer Agency’s distance of each other—this really fosters collabo- Leukemia/BMT Program in Vancouver. ration and interaction,” Smith says. “I have a fruitful collaboration with Clay. It’s “It is particularly nice on the University of Colorado Anschutz Medical Campus to have a superb group of researchers all within easy walking distance of each other—this really fosters collaboration and interaction” —clayton smith, md “Science and technology are constantly changing and there have been spectacular wonderful having him closer,” Vasiliou says. “Easy advances in treating leukemia in my lifetime,” access provides opportunities for a more produc- Smith says. “Being part of that change offers tive collaboration and spontaneous genius—both of the opportunity to use what I see in the lab which have the potential to lead to a breakthrough. when I’m seeing my patients.” That’s exciting.” 11 C3: WINTER 2012 C ASE Y C ASS Outliving the Odds IN 20 YEARS, HARRY PETERSON EXHAUSTS HIS DOCTOR’S “BAG OF TRICKS,” FINDS HOPE IN A CLINICAL TRIAL BY K I M C H R I SCA D E N 12 WWW.COLORADOCANCERCENTER.ORG WATC H F U L B UT WAI TI N G This year nearly 242,000 American men will be diagnosed with prostate cancer, the most common cancer in men. Of those diagnosed, nearly two thirds are 65 or older. Very few cases are diagnosed prior to age 40. Although most men die with and not from prostate cancer, still, nearly 30,000 lose their lives every year. At 65, Harry’s first warning signs were an elevated prostatespecific antigen (PSA) and a small growth on his prostate. After a sonogram and biopsy, the growth was found to be benign. A number of benign prostate conditions can cause an elevated PSA so Harry and his physician weren’t too concerned. “Back in the day they didn’t take a lot of specimens,” Harry recalls. “At first, my prostate cancer didn’t develop a lot of PSA; it wasn’t as elevated as the doctors were looking for.” Harry and his physician decided it was best to continue to monitor his PSA, a strategy called “watchful waiting,” to see if levels stabilized. While Harry waited, his brother-in-law was also diagnosed with prostate cancer. Unlike Harry, his PSA climbed drastically in a short period of time. He opted for brachytherapy, a type of treatment where tiny radioactive pellets are implanted in the prostate to kill the tumor. Harry had a feeling it was time for him to go back to his doctor. Could his PSA also be rising? By now it was 1996. Four years had passed since the watchful waiting began, but his PSA graphs were inconclusive. He decided it was time to have another sonogram and a set of biopsies. They were conclusive: Harry had cancer. Rather than undergo brachytherapy like his brother-in-law, Harry opted for a radical prostatectomy in early 1997. He hoped by removing the cancerous prostate he’d be cancer free. He wasn’t so lucky. “It turned out that the cancer was everywhere and it wasn’t slow-growing,” Harry says. “It was a seven on the Gleason scale.” The Gleason scale is the most common system used to grade prostate cancer. Scores range from two to 10. In order to come up with the Gleason score, a pathologist looks at the patterns of cells in the prostate tissue samples. The most common pattern of cells is given a grade of one to five. Five is the most abnormal. An additional score is given to a second common pattern of one to five and these two scores are added together to get the Gleason sum score. With a Gleason score of seven, Harry’s life expectancy was five years at best, he was told. Despite the odds, he wanted to face cancer the same way he faced work and life—with perfection. N EVE R F I N I S H E D Harry has had to get through good times and bad for more than 60 years—thankfully, he’s had his wife right by his side all those years. As a 19-year-old college sophomore at Colorado A&M, now Colorado State University, Harry married Delores, “Dee,” his high school sweetheart. “We didn’t know any better when we got married,” Harry says. “Our moms were a little upset. They didn’t think we’d make it through school.” Determined to beat the odds, Harry finished his bachelor’s. Subsequently, he was accepted into the engineering mechanics PhD program at Cornell University and was offered a teaching G LEN N AS AKAWA W hen Harry Peterson, a retired engineering professor, had his first prostate cancer scare, Bill Clinton was in his first term as president of the United States. More than 20 years have passed since President Clinton was elected and two more presidents have served, yet Harry, now 81, continues to fight prostate cancer—despite exhausting two doctors’ “bags of tricks.” “I was beyond what my urologist and oncologist Dr. David Link could offer,” Harry explains. “I was at the end of the road. I’d had such good luck with previous treatments—and then to live for 15-plus years, it was a big surprise to see everything go to pot.” Today, Harry’s not giving up hope. He’s turned to urologic medical oncologist Thomas Flaig, MD, and a clinical trial at the University of Colorado Cancer Center. “This clinical trial is a unique treatment option not available at other places in Colorado,” says Flaig. “Patients like Harry have the opportunity to participate in trials that determine the effectiveness of a new a hormonal agent for prostate cancer.” By choosing the clinical trial of a genetically targeted treatment, Harry anticipates he’ll avoid chemotherapy’s harsh side effects and outlive his latest prognosis. Opposite: Harry Peterson with Dee and his prized 1962 Morgan Drophead Coupe. Above: Xiaoping Yang, PhD (left), Thomas Flaig, MD, and Lih-Jen Su, MS, focus on genitourinary cancer translational research in Flaig’s lab at CU Cancer Center. 13 C3: WINTER 2012 Do you have an inspirational story? Tell your story at http://story.coloradocancercenter.org. position. This was the start of his career as an engineering professor, eventually leading him to the Martin Marietta Corporation (now Lockheed Martin), University of Denver and Colorado School of Mines. In the late 1960’s, Harry began researching motorcycle accidents and rider injuries through computer simulation with the U.S. Department of Transportation and a British testing lab. His research concluded the need for leg protectors and redesigned fuel systems. “Back then guys were basically riding around with tin cans between their legs that could easily catch on fire,” Harry explains. “We researched ways to prevent severe leg burns and injuries.” By 1973, Harry was an expert witness in motorcycle accidents around the country. That work, plus teaching, kept him busy up until 1995, when he retired. “I was never able to put my work aside,” says Harry. “I couldn’t stop working until it was complete. Some people call it perfectionism; it was my life.” AN OT H E R F I VE, 1 0 Y EAR S FLICKR CREATIV E CO MM ONS With determination, Harry survived the first five years post prostatectomy, despite rising and falling PSA’s. Six months of radiation helped his PSA drop, but it escalated once treatment was complete. “When he first started treatment, Harry’s urologist said if he could keep him alive for five years there would probably be better drugs available for someone like him,” Dee says. “Well, that was years ago,” Harry chimes in. “The good Lord must have been looking out for me because those five years are long gone.” In 1999, Harry started leuprolide (Lupron) injections every four months to help decrease testosterone, prostate cancer’s fuel. Harry’s PSA started to drop and stabilize. Another 10 years flew by. By late 2010, Harry’s PSA was going wild. Leuprolide was failing. Hoping to again control the testosterone, his urologist introduced bicalutamide (Casodex) into his treatment regimen. Bicalutamide is another hormonal therapy that works to block the effects of testosterone in conjunction with leuprolide. The combination therapy didn’t work. The only option his oncologist had left was chemotherapy; life expectancy at that point wasn’t great—three months to three years. His oncologist’s “bag of tricks” was empty. “There were very few options left,” Dee says. “He was at the end.” A L E S S TOX I C C H O I C E With only chemotherapy left, Harry’s oncologist contacted Dr. Flaig, who’s also the medical director of the Clinical Investigations Shared Resource at CU Cancer Center, to ask if any clinical trials were open for advanced prostate cancer patients. Harry was in luck. 14 WWW.COLORADOCANCERCENTER.ORG The PREVAIL study, a global Phase III clinical trial of an investigational drug, was enrolling patients with advanced prostate cancer. Harry qualified and enrolled in 2011. At this point, his PSA was doubling every two months. “I was certainly praying I could get on the clinical trial,” says Harry, “but I worried it was a double-blind study. I could potentially get the placebo.” The randomized, double-blind, placebo-controlled, multinational PREVAIL trial enrolled 1,680 patients with metastatic prostate cancer who had progressed despite treatment with androgen deprivation therapy, like leuprolide or bicalutamide. In addition to standard-of-care treatments (Harry stayed on leuprolide), half of the participants get a placebo and the other half get the drug enzalutamide. “We’re looking to see if we can use a less toxic hormonal pill to treat advanced prostate cancer cases where we’d traditionally use chemotherapy,” says Flaig. “Enzalutamide has already been proven to help patients live longer in more advanced settings in which the patient has already received chemotherapy. Now we want to see if it works as well if used before chemotherapy.” In the year and a half Harry’s been on the clinical trial, he’s already started to feel better and he hasn’t had to endure the harsh side effects of chemotherapy. “The difference between the side effects of taking this pill versus undergoing chemotherapy is night and day for most patients,” Flaig explains. “The pill makes sense and we need to see if we can use it earlier in the process and delay the need for chemotherapy.” With time Harry has seen his PSA drop. More time will tell if it stabilizes. Right now, he doesn’t know if he’s taking the placebo or enzalutamide. “I really owe Dr. Flaig a debt. He’s kept me alive a lot longer than was expected,” Harry says. “I don’t think I was supposed to survive this long.” “It’s gratifying to see patients respond well to new treatments,” says Flaig. “We’ll be excited to see the results of this clinical trial in the months to come.” While it’s been a long 20 years, another year or two of waiting is just a drop in Harry’s bucket. Flaig hopes the trial’s results will be published in 2013. Until then, Harry continues to simply live. LIVI N G LI F E Despite diabetes, arthritis and old age, Harry says, life’s been good. He hasn’t needed a support group. “I don’t know what I’d complain about,” he says. “For better or worse, it’s something that’s there, but it hasn’t made a big difference in our life.” When Harry’s arthritis isn’t getting the best of him, you’ll find him and a buddy tinkering with his English car collection. Today, he’s probably out working on his 1962 Morgan Drophead Coupe, a car “that outshines them all,” he says. He, too, is outshining prostate cancer. ST RY INSIDE New drugs changing prostate cancer treatment Like Harry Peterson (page 12), patients with advanced prostate cancer are directly benefiting from the development of new androgen-blocking drugs and immunotherapies. Recently, three new drugs have improved survival outcomes by curbing testosterone or training the body’s immune system to attack prostate cancer cells. E N ZA LU TA M I D E AD D S M O NTH S TO SU RV IVA L AB I RATE R O N E: AN OTH E R TE STO STE R O N E I N H I B ITO R Prostate cancer cells need androgens, like the male hormone testosterone, to grow. For prostate cancer patients with cancer that has spread beyond the prostate, hormonal therapy or androgen deprivation therapy can help prevent further tumor growth and improve quality of life. Recently, enzalutamide (Xtandi®, MDV3100) came on the market with the best survival data ever seen in prostate cancer. It lowered PSA levels, shrunk tumors and extended survival of advanced prostate cancer patients who had undergone chemotherapy by five months. “This is a major advance. Not only do we see more survival benefit than from traditional chemotherapy, but the side effects of enzalutamide are much lower,” says Thomas Flaig, MD, medical director of the CU Cancer Center Clinical Investigations Shared Resource and co-author of the study. “It provides both more benefit and less harm—you get the quantification of more life, but also see quality of life improvements.” To the body, enzalutamide looks a little like testosterone—the same pieces of cell machinery that grab testosterone grab enzalutamide instead; but unlike testosterone, enzalutamide molecules don’t tell prostate cancer cells to grow. Other therapies make the body produce less testosterone: enzalutamide ensures the body can’t use the little testosterone it continues to produce. The FDA has approved the drug for treatment of advanced castrate-resistant prostate cancer in patients who have already been treated with the chemotherapy drug docetaxel (Taxoterne). Now researchers are studying whether it can improve survival outcomes for patients, like Harry, who haven’t been treated with chemotherapy. “Enzalutamide is a key member of a half dozen new and emerging drugs and the challenge of the next five years is to discover how to best time and potentially combine these new agents. But even at this early stage, enzalutamide is a game changer,” Flaig says. Approved in 2011, abiraterone (Zytiga) has been shown to boost survival by more than three months for men whose cancer has progressed after chemotherapy with docetaxel. Abiraterone is a hormonal therapy that targets a protein called cytochrome P450 17A1—a key player in producing testosterone. The drug works in combination with prednisone to decrease the production of testosterone in the testes, adrenals and in the cancer itself. This class of drugs is called androgen biosynthesis inhibitors, and abiraterone was the first of its type approved by the FDA. Unlike chemotherapy, these new drugs kill fewer healthy cells along with the cancerous cells and so have fewer side effects. “Targeting cells’ androgen receptors is a new and exciting development in the field of prostate cancer therapy,” says E. David Crawford, MD, head of urologic oncology at CU Cancer Center. “As these new drugs make their way from the lab to clinic, we expect the ability to offer androgen antagonists to patients whose cancers have resisted other treatments.” To learn more about prostate cancer treatments at CU Cancer Center, visit www.uch.edu/conditions/cancer/prostate-cancer/ To search for a cancer clinical trial, visit www.uch.edu/conditions/cancer/research/ research_trials/ P R O STATE CAN C E R’ S F I R ST I M M U N OTH E RAPY For men who have advanced prostate cancer that is not responding to hormonal therapies, researchers are advancing the use of a new class of drugs known as immunotherapies, including the drug Provenge®. Provenge trains the body’s immune system to attack prostate cancer cells. The treatment involves removing the patient’s own white blood cells, mixing the cells with a drug designed to target prostate cancer cells, and then re-infusing the treated blood into the patient. The treatment is repeated three times over the course of a month. In 2010, data from the IMPACT trial showed patients who received Provenge lived on average more than four months longer than men who received the placebo treatment. While Provenge, Abiraterone and Enzalutamide are not cures, they offer hope to patients who previously exhausted all treatment options. “Even without the addition of any more drugs, we may now have the tools that in combination will allow us to extend the survival prognosis of a prostate cancer patient long enough to make prostate cancer a disease a patient is more likely to die with than from,” Crawford says. —Kim Chriscaden and Garth Sundem 15 C3: WINTER 2012 TOBACCO TAX SPENDS MONEY TO SAVE MONEY …AND LIVES WITH ECONOMY’S CLIMB, 35 AMENDMENT AGAIN FUNDS PREVENTION PROGRAMS BY E R I K A MATI C H F rom 2004 to 2008, money from the Amendment 35 tobacco tax funded chronic disease prevention programs. Then the recession hit and the state redirected this money to other urgent needs. Now, with the economy’s slow climb from the doldrums, millions of dollars from Colorado’s tobacco tax are once again flowing. Researchers in cancer prevention programs at the University of Colorado Cancer Center are hopeful the money will impact the state’s cancer rates—and save both lives and health care costs in the long run. “The good news is programs to prevent cancer are being funded again,” says Tim Byers, MD, MPH, associate director of cancer prevention and control at CU Cancer Center and associate dean of public health practice at the Colorado School of Public Health. For example, CU Cancer Center projects that screen uninsured individuals for colon cancer, help smokers quit, and identify patients at risk for hereditary breast and colorectal cancer are rediscovering their footing due to returned Amendment 35 funding. “The competitive grants given because of Amendment 35 mean the best of the best evidence-based programs can once again compete for funding,” Byers says. “As a result, hundreds of people won’t get cancer and the health care system won’t have to bear those costs.” 16 WWW.COLORADOCANCERCENTER.ORG BALAN C IN G TH E SM OKIN G BURDE N Smokers tend to tax the health care system, so the system should in turn tax smokers. That was the gist of the thinking in 2004, when 61 percent of Colorado voters approved Amendment 35 to increase taxes on cigarettes and other tobacco products. The thinking was right: Annual health care costs in the United States directly related to smoking are more than $1 billion. Approximately $425 million in income and produc tivity is lost every year due to premature death caused by smoking. And tobacco-related illnesses are the leading cause of preventable death in Colorado. Tax revenue went to programs that sought to balance these numbers—to prevent these preventable deaths and save the health care system the money it would eventually spend taking care of these smokers. For example, the statute requires 16 percent of tobacco tax revenues to be used for school funding of tobacco education programs aimed at keeping youth from smoking, smoking cessation programs and programs to reduce exposure to secondhand smoke. Another 16 percent goes to prevention, early detection and treatment of cancer, cardiovascular disease and chronic pulmonary disease. CU Cancer Center got a slice of each of these funds—and came to depend on these monies to keep the lights on in many of the Center’s prevention and control programs. When the economy went south, Colorado legislators declared a fiscal emergency. From 2009 to 2011 Amendment 35 funds were down in general—fewer people could afford to smoke. And these reduced funds were redirected to cover expanding Medicaid costs. Cancer prevention programs like CU Cancer Center’s Colorado Colorectal Screening Program saw their budgets slashed—free screenings were reduced and research projects went into maintenance mode. CANCER SCREENING INFORMATION Colorado Colorectal Screening Program participating clinics 866-227-7914, www.colonscreen.coloradocancercenter.org Women’s Wellness Connection 866-951-WELL (9355) Metro Community Provider Network 303-360-MCPN (6276) O U T O F HI B E R NATI O N The economy goes up, tax revenues go up, prevention and control programs go up. Hopefully speaking, smoking and cancer rates will go down. With the first now gaining traction, CU Cancer Center researchers are starting to see the other three fall in line. Arnold Levinson, PhD, MJ, a tobacco control expert at the CU Cancer Center, is the scientific director on a new three-year, $600,000 grant to design, implement and evaluate smoking cessation treatment programs for tobacco-using patients in the University of Colorado Health system. The project—a collaboration between CU Cancer Center and University of Colorado Hospital (UCH)—brings together the academic expertise of Levinson’s research group with system-wide access to patients in three University of Colorado Health hospitals: UCH, Poudre Valley Hospital and Medical Center of the Rockies. “We hope our initiative will serve as a model for other hospitals,” Levinson says. Byers hopes the program will directly result in quitting. “About 17 percent of the population in Colorado smokes,” he says. “There is really no reason we can’t continue to drive down that number.” “Hopefully, by identifying high-risk patients, clinics can prioritize their already limited resources for subsidized screenings,” she explains. Colorado Generations matches medically underserved Coloradans with genetic counselors who can help assess cancer risk, coordinate testing and make screening recommendations for those at especially LO W ERY high risk for hereditary cancers. “The goal is to increase awareness about family history and hereditary cancer risk among patients and their providers,” Lowery says. “We want them to know what it is and whether it may affect them so that they can get appropriate care and make informed, pro-active decisions about their health.” Colorado Generations refers patients to Women’s Wellness Connection for free breast cancer and cervical cancer screenings. It also refers patients to the Colorado Colorectal Screening Program (CCSP)—another Amendment 35-funded project at CU Cancer Center, which through June 2011 had screened more than 13,000 Coloradans at 65 community health clinics and detected 112 cancers. “The program saves millions in medical costs by preventing colorectal cancer,” says Andrea Dwyer, CCSP Program Manager. “And you can’t put a price tag on the lives saved by those whose cancers were caught early or completely prevented.” With the loss of Amendment 35 money, the CCSP had to cut way back. Now the money has returned. “We were awarded nearly $3 million dollars this year in the state’s competitive grants program to rebuild the program infrastructure and screen several thousand people.” Amendment 35 money goes up, cancer goes down. Byers, Bunn, Levinson, Lowery, Dwyer and their CU Cancer Center colleagues hope that 2012 and 2013 are only the start. LY NN C LARK At the same time, Byers and Cancer Center colleague Paul Bunn, MD, joined the American Cancer Society’s effort to encourage state legislatures to preserve Amendment 35 money. Their efforts worked. Today, Colorado’s economy is recovering and Amendment 35 funding is being restored. In fiscal year 2012-2013, the state of Colorado predicts it will receive approximately $140 million in tax revenue from Amendment 35—about $46 million of which will be available to agencies working to prevent cancer—agencies like CU Cancer Center. In addition to funding tobacco cessation and education programs, Amendment 35 sets aside money for research and treatment grants. Jan Lowery, PhD, MPH, CU Cancer Center investigator and assistant professor of epidemiology at the Colorado School of Public Health, is benefitting from one of these grants—and her work could soon benefit all Colorado residents. Lowery’s project, called “Colorado Generations” (for which she teamed up with Metro Community Provider Network and Plains Medical Center), is all about maximizing thin resources. Who should undergo costly advanced cancer screening? Well, the people who are at the greatest risk of developing the diseases. “It’s critical that we identify people who are at risk for here ditary cancer because their risk for developing cancer may be as high as 80 percent,” Lowery says. “This project will help clinics identify their patients that, due to their family history, are at increased risk for cancer and in need of cancer screening.” GL ENN ASAK AWA BEYO N D T O B ACCO The Colorado Colorectal Screening Program at CU Cancer Center has screened more than 13,000 Coloradans at 65 sites across the state. 17 C3: WINTER 2012 S U P P O R T E R F CUS Neighborly Commitment C OURT E SY OF C ANC E RC URE CANCE R SU RVIVOR S, N E IGH BOR S “ALLOW GR EAT R E S EARCH TO HAPPE N” FOR 16 YEAR S BY K I M C H R I SCA D E N Midge Wallace, Carolyn Fancher and Nina Ahbe A fluke phone call from their daughters at are more than friends and neighbors. They’re also Miami University in Ohio brought Carolyn and Nina breast cancer survivors committed to funding cancer together. It turned out that both Carolyn’s and research and spurring others to do the same. Nina’s daughters were starting their freshman year Affected by breast cancer in the 1990’s, Midge and living in the same dorm. It wasn’t long after and Carolyn know firsthand the impact the disease that Nina and Carolyn became friends—and Nina has on patients and families. In 1996, not wanting became a breast cancer survivor. their children or grandchildren to have to go through After Nina’s treatment was completed she and the same experience, Midge and Carolyn founded her husband joined CancerCure. Two years ago, CancerCure, a membership group for donors inter- she became CancerCure’s co-chair with Midge. ested in supporting cancer research at University “When you’ve been touched by cancer, like of Colorado Cancer Center. Midge, Carolyn and I have, you want there to be “Our mission is really to spread the word about more research so that new discoveries are made, the CU Cancer Center, what a National Cancer potentially impacting future generations,” Nina says. Institute-designated cancer center is, and how Now 16 years later, Midge, Nina, Carolyn and important it is to have this high level care and other CancerCure members have raised nearly research here in Colorado,” Midge says. $1.5 million through individual gifts. The members When they founded CancerCure, Midge was Nina and Midge with one of CancerCure’s founding members, Mary Lee Beauregard at the check presentation in May 2012. have funded seed pilot grants for young research- Nancy Stewart, vice president of community only interested in funding breast cancer research; ers, summer student cancer fellowships, critical relations at AMC Cancer Fund. “Historically, however, she quickly learned that a rising tide floats research equipment and a melanoma research the investigators of what was the AMC Cancer all boats—discoveries in one cancer are frequently group, among others. Research Center were at the forefront in this area relevant to others. One hundred percent of their funding goes “At first I only wanted to focus on breast towards cancer research in Colorado and is used at cancer since my mother, sister and I have had the the discretion of the CU Cancer Center director. disease,” says Midge. “After meeting and spending of cancer research. We believe the endowment is a wonderful way to honor our legacy.” Because the majority of research funding goes to science aimed at treating cancer rather than pre- time with researchers, I realized there are so many Shifting Focus venting it, CancerCure and AMC Cancer Fund will crossovers to multiple cancers.” Last fall, CU Cancer Center Director Dan fund projects aimed at reducing cancer incidence, Theodorescu, MD, PhD, challenged CancerCure morbidity and mortality, as well as improving the Another Survivor to undertake a larger fundraising initiative: establish quality of life for cancer patients. These projects Ten years ago, Nina Ahbe and her family moved a premier prevention and control program, headed will be funded using investment income from the to Colorado and bought a house in the same by an endowed chair—a five-year, $1.5 million endowed chair. neighborhood as Carolyn and Midge. She was commitment. diagnosed with breast cancer shortly after, having “This is the first time the director came to us D ANA Mc GRATH not met either of the women. “In our world today we don’t allow for enough great research to happen,” Midge says. ahead of time,” Midge says. “Dr. Theodorescu felt “Because we have an NCI-designated compre- the endowed chair for cancer prevention and con- hensive cancer center in Colorado, I’m excited to trol was one of the Cancer Center’s greatest needs. support the research CU Cancer Center does so We decided to accept his request and commit to that we can eradicate cancer from our and our raising $750,000 over the next five years.” children’s lives.” AMC Cancer Fund, the CU Cancer Center’s fun- Nina Ahbe and Midge Wallace present an initial $250,000 check to the CU Cancer Center on behalf of CancerCure. 18 WWW.COLORADOCANCERCENTER.ORG draising partner, is collaborating with CancerCure CancerCure welcomes new members throughout to raise the additional $750,000 needed to fund the the year and hosts two annual events for its general CancerCure/AMC Cancer Fund Endowed Chair for and patron members. General memberships are Cancer Prevention and Control. In May 2012, Nina $100 and patron level memberships are $750 and Midge presented an initial $250,000 check to annually. Learn more about membership levels at the Cancer Center on behalf of CancerCure. www.wearecancercure.org or contact Nina Ahbe “AMC Cancer Fund is honored to partner with CancerCure to establish an endowed chair,” says or Midge Wallace at email@example.com. N E W S KIM C H RISC ADE N C O M M U N I T Y S AV E T H E D A T E MARCH 7 – COCKTAILS FOR A CURE Join AMC Cancer Fund on March 7, 2013 for the 4th annual Cocktails for A Cure Women’s Event benefiting CU Cancer Center. Bring a girlfriend and sip on a signature cocktail, peruse the silent auction or take a chance at the wall of wine. Most importantly, enjoy an enlivening experience celebrating Colorado women and supporting the research and treatment of women’s cancers at CU Cancer Center. RESEARCHER LEADS TWO-DAY FRONT RANGE RIDE FOR CANCER RESEARCH FIRST YEAR RIDE HOSTS 35 RIDERS, RAISES $10,000 When Scott Cramer, PhD, professor of pharmacology, prostate cancer researcher and co-director of the New joint fundraising team, location Hormone Related Malignancies Program at the University of Colorado Cancer Center, moved to Colorado and name in 2013 a year ago, he instantly organized his life around cycling. In January, the AMC Cancer Fund will be Besides commuting 16 miles to work every day, Cramer started planning the Cancer Center’s first changing its name to the University of Colorado group bike ride to support cancer research—an event he assumed already existed. Cancer Center Fund. Partnering with CU “When I first moved to Colorado I was surprised there wasn’t an organized ride for the University of Foundation fundraisers dedicated to the Colorado Cancer Center,” Cramer says. “I figured there would be with how big cycling is in Colorado.” Cancer Center, CU Cancer Center Fund will be That didn’t stop Cramer from starting his own. In September, Cramer and more than 30 other riders located on the University of Colorado Anschutz piloted the Cancer Center’s first Front Range Ride taking riders 110 miles from the CSU Animal Cancer Medical Campus. Their new address is Center to CU-Boulder and then on to the CU Anschutz Medical Campus. The riders raised nearly $10,000 13001 E. 17th Place, MS F500, Aurora, CO, for cancer research. 80045. Stay tuned for a new website, brand “The goal is to eventually make this a fundraising event that would be the signature event for the Cancer and logo. The ride linked four of the Cancer Center’s nine consortium members: Children’s Hospital Colorado, University of Colorado Hospital, CSU Animal Cancer Center and CU-Boulder. The Cancer Center consortium unites Colorado’s basic, translational and clinical cancer research at three universities, five medical centers and DRIVERS SIDE one health maintenance organization. CACTUS STEVE Z PHOTOGRAPHY Center, while highlighting our unique consortium,” he says. University of Colorado Hospital Mobile Mammography Make your appointment at UCH.EDU/MAMMOGRAM or call 720.848.1030 Dinner in White pops up in downtown Denver Downtown Denver was blanketed in a sea of white as the 3rd annual Dinner in White, hosted by AMC Cancer Fund, popped up near Denver Union Station. The annual event hosted 350 guests and brought in more than $38,000 for cancer research at CU Cancer Center. NEW “PINK LIFE SAVER” HITS THE STREETS, PROVIDES BREAST CANCER SCREENINGS The top two reasons women don’t get annual mammograms are time and convenience. In an effort to overcome those excuses, University of Colorado Hospital, CU Cancer Center’s patient care partner, has created a mobile mammography coach named “The Pink Life Saver.” The Pink Life Saver was unveiled to the public for the first time on October 16 at the annual Men for the Cure event. Funds raised by Men for the Cure, along with money donated by King Soopers, paid for the unit, which is fully equipped to provide breast cancer screenings to women around the metro Denver area. Patients are able to schedule appointments for screenings in The Pink Life Saver, as the unit travels to UCH clinics and The Little Clinic at select King Soopers stores, one day a week. If the service is successful, the hospital plans to expand it to corporate clients. To find out where The Pink Life Saver is going to be or to schedule an appointment, call 720-848-1030. 19 C3: WINTER 2012 UNIVERSITY OF COLORADO DENVER WI NTER 2012 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: Kim Chriscaden | 303-724-0114 | Kimberly.Chriscaden@ucdenver.edu Contributing Writers: Garth Sundem, Erika Matich Photos: Glenn Asakawa, Casey Cass, Lynn Clark, Dana McGrath, Steve Z. Photography The CU Cancer Center Consortium Members UNIVERSITIES Colorado State University University of Colorado Boulder University of Colorado Denver INSTITUTIONS University of Colorado Hospital Children’s Hospital Colorado National Jewish Health Denver Health Medical Center Denver Veterans Affairs Medical Center Kaiser Permanente Colorado Visit us on the web: www.coloradocancercenter.org The CU Cancer Center is dedicated to equal opportunity and access in all aspects of employment and patient care. T H E The accelerating pace of cancer discovery makes the next six months a critical, exciting and hopeful time in our fight against the disease M E S S A G E S ix months ago when we sent the previous issue of this It’s been a big six months. magazine, we didn’t know the spread of bladder cancer With the involvement and support of our community, the is dependent on androgens like testosterone. As you’ll FROM THE DIRECTOR DAN THEODORESCU, MD, PhD University of Colorado Cancer Center looks forward to an even read in this issue of Collaborating to Conquer Cancer, we now bigger six months ahead. In partnership with MD Anderson, we hope to eventually target bladder cancer with anti-androgens have a new grant to develop drugs for bladder cancer. Our lead- like those used to treat prostate cancer. Six months ago, the ing work in targeted lung cancer treatments continues. Our clini- drug enzalutamide was still investigational. Now due in part to cal trials program continues to offer tomorrow’s drugs to today’s clinical trials at the CU Cancer Center, the drug has earned FDA patients. And we are taking major steps in our understanding approval and is being used to extend the lives of patients with of cancer as many individual but related diseases, defining the advanced prostate cancer. We were recently instrumental in discovering melanoma stem cells and at the Charles C. Gates Center for Regenerative Medicine and Stem Cell Biology, we just opened a clinical trial of a drug targeting cancer stem cells. In the past six months, we cut the ribbon on a major expansion of the Anschutz Cancer Pavilion at our clinical care partner, University of genetic signature of a patient’s tumor and using “The Cancer Center represents the confluence of expertise, technology, experience and compassion...” Colorado Hospital, opening 42,000 square feet that signature to match patients with the most effective treatments. The Cancer Center represents the confluence of expertise, technology, experience and compassion from our consortium sites that encompass nearly all federally-funded cancer researchers in the state of Colorado. Investigators’ home sites include CU Denver, CU-Boulder, Colorado State University, of new space and dozens of new exam and treatment rooms. University of Colorado Health, Children’s Hospital Colorado, On the heels of our partnership with Poudre Valley Health, we’ve Denver Health, Denver VA Medical Center, National Jewish Health forged a new alliance with Memorial Health System, expanding and Kaiser Permanente Colorado. Members at these institutions the reach of our care from Fort Collins to Colorado Springs and create a critical mass—with your help, we can not only continue beyond. And in the last six months, the National Cancer Institute the trajectory of cancer discovery but accelerate that pace. renewed our prestigious designation as a comprehensive cancer center, recognizing our excellence in all aspects of the search for cures, from basic lab research to patient care. 20 WWW.COLORADOCANCERCENTER.ORG Here’s to the next six months.