C3: Collaborating to Conquer Cancer
The University of Colorado Cancer Center's magazine - C3: Collaborating to Conquer Cancer, Spring 2012 edition.
C O L L A B O R AT I N G T O C O N Q U E R C A N C E R S P R I N G 2 012 Cancer Arrow 12: TOUGH AS NAILS | 15: BATTLE OF THE BULGE 10: Q&A WITH BORSIKA RABIN, PhD, MPH, PharmD | 11: C3 MD ANA OTON 18: SUPPORTER FOCUS ON THE MORGAN ADAMS FOUNDATION S P L I T T I N G T H E ANSCHUTZ MEDICAL CAMPUS MAJOR STUDY STOPS BLADDER CANCER FROM METASTASIZING TO LUNGS The diagnosis of localized bladder cancer carries an 80 percent five-year survival rate, but once the cancer spreads, the survival rate at even three years is only 20 percent. A major study led by CU Cancer Center Director Dan Theodorescu, MD, PhD, not only shows how bladder cancer metastasizes to the lungs but pinpoints a method for stopping this spread. Specifically, the study shows that versican, a protein involved in cancer cell migration, is a driver of lung metastasis and that high levels of versican are associated with poor prognosis in bladder cancer patients. The study is also the first to show that when a cancer cell makes the protein RhoGDI2, it reduces the cell's production of versican, thus blocking the ability of the cancer cell to grow in the lungs. TH EO D O R ES C U "For a decade, we've known that the major challenge of treating bladder cancer is treating or preventing the metastatic form of the disease. This study represents an advance in the latter: By preventing the spread of bladder cancer to the lungs, we could improve patient survival," says Theodorescu. N3WS FOUR NEW DRUGS W I L L C H A N G E P R O S TAT E CAN C E R CAR E After a decade and a half of near stagnation, four new drugs could make advanced prostate cancer a chronic illness instead of a terminal disease, says E. David Crawford, MD. First is the drug denosumab, which Crawford says can prevent bone fractures, osteoporosis, and perhaps hold off the occurrence CRAW FO RD of bone metastasis in prostate cancer patients. Second is the drug Alpharadin, which is one of a novel and exciting class of "radiopharmaceu- WOMEN NOT FOLLOWING THROUGH WITH RECOMMENDED BREAST SCREENING MRI A study of 64,659 women found that while 1,246 of them were at high enough breast cancer risk to recommend additional screening with MRI, only 173 of them returned to the clinic within a year for the additional screening. "It's hard to tell where, exactly, is the disconnect," says Deborah Glueck, PhD, investigator at the CU Cancer Center. But no matter the disconnect, the result is clear: women who should be getting breast screening MRIs are not. Along with her PhD student, John Brinton, Glueck worked with doctors at the Invision Sally Jobe Clinics in Denver to gather the needed data. According to Glueck and Brinton, the most fundamental and overarching question is whether the benefits of MRI screening for women at high risk for breast cancer, in fact, outweigh its high monetary, medical and psychological costs. Follow-up studies will chip away at this question, including a planned study in which the researchers will see if informing high-risk women directly about the screening recommendation, instead of depending on primary care physicians to relay this information, will improve screening adherence. ticals" � drugs that emit radiation and allow doctors to precisely deliver radiation to tumor sites. Third, the drug Prostvac is the first "immunotherapy" drug used for the treatment of cancer. The drug acts like a vaccine, priming the immune system to recognize and thus fight against prostate cancer cells. Finally, the drug abiraterone acetate completely suppresses the body's ability to make testosterone, which many prostate cancers need in order to grow. "Before we just had hormone therapy, then we got chemo, and each therapy we added packed on another couple months of survival. Now with these news drugs we're tacking on even more time. The light at the end of the tunnel is the hope that we'll turn this into a chronic disease, and now we might have the tools that in some combination will do it," Crawford says. CANCER CLINICAL TRIALS EXPAND AT THE DENVER VA -- A BIG WIN FOR COLORADO VETERANS Although the Denver Department of Veterans Affairs Medical Center has been a member institution of the CU Cancer Center since the Center's inception in 1988, the partners recently took another important step, expanding cancer clinical trials collaborations to offer early-stage trials of new drugs at the VA. "When I came here almost four years ago, it struck me that while we were offering cancer clinical trials for people from out of state with all kinds of insurance, we weren't offering those same options to our veterans," says Antonio Jimeno, MD, PhD, director of D R . J IM E NO W I TH PATI EN T, K ATR I N A LYNN CL ARK GLBT SMOKERS IN C O LO R A D O N OT T H I N K I N G ABOUT QUITTING Gay, lesbian, bisexual and transgendered Coloradans who smoke are not thinking about quitting or getting ready to quit, and a quarter are uncomfortable approaching their doctors for help, according to a CU Cancer Center study. "Among most smoking populations, we almost always find 20 percent getting ready to quit and another 40 percent are thinking about quitting," says Arnold Levinson, PhD, MJ, investigator at the CU Cancer Center. "But the rates from our study were half of what we expected." For more than 70 percent of the GLBT smokers who were surveyed, quitting was not on their agenda. And in contrast with low rates in other smoking populations, more than 25 percent of GLBT respondents were uncomfortable asking their doctor for smoking cessation advice. the Head and Neck Cancer Medical Oncology Program at the CU Cancer Center. While the Denver VA has access to many cancer clinical trials, some of the most exciting studies incorporating new drugs still under early investigation were not available to their patients. This unique collaboration dramatically expands their treatment options. "This has been an extraordinary example of how, when people set out to do the right thing, no barriers can stop us. A huge team of people from both sides, including clinical coordinators, nurses, administrators, and docs worked relentlessly to make it happen. We're all really, really proud of this," Jimeno says. 2 WWW.COLORADOCANCERCENTER.ORG of these kids will develop melanoma, the most serious form of skin cancer, killing 48,000 people every year, worldwide. Now look at these kids again--which are at highest risk? You can't tell, but a CU Cancer Center study shows that UV photography might provide important information about risk, not visible to the naked eye. The study is the first to show that the amount of sun damage in UV photographs taken of a large cohort of 12-year-old's correlated with known melanoma risk factors including freckles, fair skin, red hair and light eye color. "Primary care physicians could use UV photographs with children and young teens to provide better sun protection counseling," says Ryan Gamble, MD, the study's first author and postdoctoral researcher in the lab of Robert Dellavalle, MD, PhD, MSPH, CU Cancer Center investigator. "Before middle school kids think about tanning, we want them to see these pictures," Dellavalle says. With UV photographs and sun prevention "much of the occurrence of the disease and its complications can be prevented" in the high-risk population, Gamble says. U V P H O TO G R APHY MI GHT PRO VI DE I M P O RTA N T I NFO RMATI O N ABO UT S K I N C A N C ER RI SK. LARGEST-EVER STUDY OF CHILDHOOD ALL SHOWS IMPROVING SURVIVAL A 21,626-person study led by CU Cancer Center investigator Stephen Hunger, MD, found that the five-year survival rate for children and adolescents with acute lymphoblastic leukemia (ALL), the most common childhood cancer, improved from 83.7 percent in those diagnosed during the years 1990 to 1994 to 90.4 percent for those diagnosed in the years 2000 to 2005. "The improved survival is due to using existing drugs better, not because of the introduction of new drugs," says Hunger. "We're indebted to all the families who chose to join these clinical trials, allowing us to optimize these combinations. "In the early 1960s this disease was incurable," Hunger says. "Then in the late 1960s, the cure rate was 10 percent. Now almost 90 percent of children and adolescents diagnosed with ALL will be cured. Still, a 90 percent survival rate is little consolation to the 10 percent of families whose child doesn't survive. There's still more work to be done." For Hunger and other members of the Children's Oncology Group, "almost all" is not enough. GRAPE SEED EXTRACT KILLS HEAD AND NECK CANCER CELLS, LEAVES HEALTHY CELLS UNHARMED Nearly 12,000 people will die of head and neck cancer in the United States this year and worldwide cases will exceed half a million. A study led by CU Cancer Center investigator Rajesh Agarwal, PhD, shows that in both cell lines and mouse models, grape seed extract kills head and neck squamous cell carcinoma cells, while leaving healthy cells unharmed. "It's a rather dramatic effect," says Agarwal, "and it depends in large part A G A R WAL on a healthy cell's ability to wait out damage. "Cancer cells are fast-growing cells," Agarwal says. "Not only that, they are necessarily fast growing. When conditions exist in which they can't grow, they die." Grape seed extract creates these conditions that are unfavorable to growth. Specifically, Agarwal shows that grape seed extract both damages cancer cells' DNA (via increased reactive oxygen species) and stops the pathways that allow repair (as seen by decreased levels of the DNA repair molecules Brca1 and Rad51 and DNA repair foci). The Agarwal Lab hopes to move in the direction of clinical trials of grape seed extract, potentially as an addition to second-line therapies that target head and neck squamous cell carcinoma that has failed a first treatment. NEW DEVICE USES GOLD NANOPARTICLES TO TEST FOR LUNG CANCER The metabolism of lung cancer patients is different from the metabolism of healthy people. And so the molecules that make up cancer patients' exhaled breath are different too. A new device pioneered in part by CU Cancer Center investigator, Fred R. Hirsch, MD, PhD, uses gold nanoparticles to trap and define these molecules in exhaled breath, discovering not only if a lung is cancerous, but if the cancer is small-cell or non-small-cell, and adenocarcinoma or squamous cell carcinoma. "This could totally revolutionize lung cancer screening and diagnosis," says Hirsch. "The perspective here is the development of a non-traumatic, easy, cheap approach to early detection and differentiation of lung cancer." Subjects simply exhale into a bag, which separates superficial exhaled breath from breath that originated deeper in the lungs. And then this deep breath is analyzed by an array of gold nanoparticle sensors. "You can imagine standing in the grocery store and having high-risk people blow into a bag," Hirsch 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. C OURT E SY OF T H E AME RIC AN AC ADE MY OF DE RMAT OLOGY 90.4 5 -Y E A R S U R V I VA L R AT E % UV PHOTOGRAPHS OF 12-YEAR-OLDS SHOW SKIN CANCER RISK Look at a middle school assembly--during their lifetime one in 50 3 C3: SPRING 2012 Cancer Arrow BY GA RT H S U N D E M SPLITTING THE 4 WWW.COLORADOCANCERCENTER.ORG BULL' S E Y E /GE T T Y IMAGE S Biomarkers and the precise therapies that target them will cure cancer by degrees--and change the way drugs do business. I n the 2010 film adaptation of Alice in Wonderland, the Red Queen inspects a line of frog footmen to determine which frog ate her tarts. All of these footmen sweat and shiver, but it's the bit of jam at the corner of one footman's mouth that gives him away. Off with his head! This is a biomarker--a physical clue that marks something different from its surroundings. In Alice in Wonderland, the jam biomarker makes the unfortunate frog footman a target, and the Red Queen is his destructor. Researchers at the University of Colorado Cancer Center are using similar biomarkers to paint jam bull's-eyes on cancer. "We've all heard cancer called the `Big C,' " says Dan Theodorescu, MD, PhD, director of the CU Cancer Center. "But it turns out that it's actually made up of literally thousands of little C's, all of which share characteristics like unchecked growth, but beyond which may be as different as cats and dogs. They're both mammals, but you can't expect them both to come when you whistle." The realization that the "Big C" is many little C's, each perhaps identified by distinct, individual biomarkers, also means that the other Big C--"Cure"--is likely to be a series of singles that pick off each subset in turn, rather than the home run that ends the disease entirely. "It's basically peeling an onion," Theodorescu says. "Once you peel off the layer of ALK-positive lung cancer [as the CU Cancer Center did in 2011], you find another layer. Peel off that next layer of cancer and you're onto another until eventually you've peeled away the disease entirely, one subset at a time." This rethink of cancer as "cancers" is driving a sea change not only in new, targeted treatments but in how these treatments are developed. But let's start with jam--what are the biomarkers of cancer? O N C E R E S E A R CH ER S D I S C OV ER A B I O M A R K ER , T H E Y C AN TA R G E T I T . SOMETIMES THE S I G N AT U R E O F A D I S E A S E IS A SPRINKLING OF HINTS T H R O U G H O U T A C AN C ER CELL'S GENOME. CAN C E R B I O M AR K E R S--F LAVO R S O F JAM A cancer biomarker can be as simple and well-known as the prostate-specific antigen (PSA) test for prostate cancer. A man with high or increasing levels of PSA in his blood has jam on his cheek--off with his prostate! (Caution: oversimplification alert, but you get the point.) Another well-known biomarker is the Philadelphia chromosome--a mutation that occurs when chromosome number 9 breaks off a bit of itself and inserts it in chromosome number 22. This Philadelphia chromosome (now without the speed governor that should limit its growth) is present in 95 percent of people with chronic myelogenous leukemia (CML). Once researchers discover a biomarker, they can target it, which is what the drug Gleevec does in CML, attaching specifically to these cells' broken speed governors. Before Gleevec, CML patients died; after Gleevec, a recent New England Journal of Medicine study shows that 95.4 percent of CML patients are alive eight years after diagnosis. Researchers around the country are trying to duplicate this success story. What will be the next Philadelphia chromosome and what will be the next Gleevec? Sometimes, though, the answer isn't quite so simple; sometimes the definition of a disease rests not on the back of one chromosome but on many. Sometimes the signature of a disease is a sprinkling of hints throughout a cancer cell's genome. Dan Theodorescu hunts these hints. 5 C3: SPRING 2012 CA N C E R AS TH E SU M O F ITS M UTATI O N S First some background: the National Cancer Institute (NCI) maintains 60 lines of cancer cells. In the late 1980s, these cells were taken from 60 real human breast, lung, and brain and other human tumors, and since then the NCI has carefully kept the cell lines alive. Like pulling off a piece of sourdough starter for a loaf of bread, when researchers want to experiment on cancer cells, they can split off cells from these 60 lines. What kills cancer? Well, researchers have now tested more than 110,000 chemicals on these 60 cell lines and have a pretty darn good idea of what kills them. But there's a twist: Theodorescu specializes in bladder cancer, and there are no bladder cancer cells included in the NCI-60. How can you know what drugs work against bladder cancer, or for that matter any cancer not represented in the NCI-60, if the cells haven't been hit with the 110,000 drugs? One method would be to get bladder cancer cells, blast them with the drugs and see what happens. (Can you spare many millions of dollars?) Another method would be to look at historical data of how bladder cancers with certain genetic signatures responded to the drugs used to treat them. (If you have the data, Theodorescu and other bladder cancer researchers would love to see it.) The third method is the innovative approach that Theodorescu and his co-authors call COXEN, which stands for CO-eXpression ExtrapolatioN. Basically, COXEN looks at cancers not as "breast" and "bone" and "brain" but as signatures of the genes that are mutated in each. In other words, COXEN boils down a cancer cell to the 20-or-so genes that define it--can 20 important genes predict how a tumor will respond to a drug? There are three P's when it comes to the uses of cancer biomarkers: predisposition, prognostic and predictive. PREDISPOSITION: In breast cells, the gene BRCA1 is responsible for repairing damaged DNA or killing cells that can't be repaired. When BRCA1 itself is damaged, a person is more highly predisposed to develop breast cancer. PROGNOSIS: breast cancers that don't depend on estrogen, progesterone or something called HER2 are termed "triple negative" and carry a less favorable prognosis than their hormone-dependent cousins. PREDICTIVE: The genetic biomarker of what's called an "ALK-EML4 fusion gene" predicts strong lung cancer response to the drug crizotinib. --Dan Theodorescu, MD, PhD C OX E N K I C K S TI R E S You can bet Theodorescu and his coauthors took the question into the lab to kick the tires. First, they mined the NCI-60 to discover which 20-ish genes predict response or resistance to the drugs cisplatin and paclitaxel. Great--and once they had the genetic signature of cancers that were responsive and resistant, they wondered if the same 20 genes might predict response or resistance to these drugs in bladder cancer patients. In 85 percent of cases with cisplatin and 78 percent of cases with paclitaxel, the answer was yes. Consider the tires kicked. Theodorescu did a similar test with breast cancer. Could his group use biomarkers to predict relapse after tamoxifen? Again, Theodorescu mined the NCI-60 to discover which genes predicted response to the drug--which ones were most "up" or "down" in successful and unsuccessful patients. And patients on a clinical trial for the drug had their tumors genetically sequenced before treatment. Would patients whose biomarkers predicted drug resistance relapse? In 71 percent of cases, yes. Based on the signature of these important genes, Theodorescu could predict fairly accurately who would relapse after tamoxifen. While it's nifty to have a genetic taxonomy for cancer that predicts how a patient will respond to any given drug, it's perhaps even niftier to use a disease's genetic signature to pick the best drug. Here's how COXEN does it: We know what drugs kill the NCI60. We know the genetic signatures of these NCI-60. And we can fairly easily discover the genetic signature of any given cancer. If a tumor's genetic signature is similar to that of cells in the NCI-60, you can predict what drugs will kill it. By matching the biomarker profiles of bladder cancer to similar cancer cells in the NCI-60, COXEN predicts a strong bladder cancer drug should be imidazoacridinone-- sure enough, when Theodorescu and his team hit bladder cancer cells with imidazoacridinone, more than 60 percent were killed (compared with only 22 percent for the most common bladder cancer drug, cisplatin). Theodorescu hopes imidazocridinone, as identified by the COXEN model, may become a new anchor drug for the treatment of the disease. 6 WWW.COLORADOCANCERCENTER.ORG CAN C E R S I G NATU R E S C R O S S S P E C I E S So biomarkers allow us to crystalize just the important parts of a disease's genetic signature and match the signature to similar genes from the NCI-60, which then allows us to predict drug response or pick the best drug--targeted not just at cancer in general, and not just at the cancer's location, but at the very genes that make up the disease. Dawn Duvall, PhD, and other researchers at the Colorado State University Animal Cancer Center (a member of the CU Cancer Center consortium) asked another interesting question: could COXEN cross species? In other words, do the genetic signatures of specific cancers trump the difference between humans and our best friends? There's an interesting intersection of dogs and humans that allowed Duvall and her team to answer that question. That intersection is bone cancer--osteosarcoma. It turns out that on a genetic level, you can't tell a K9 osteosarcoma from a human one. And in the realm of osteosarcoma, dogs have the drop on us. "Only about 800 osteosarcomas are diagnosed in humans every year," Duvall says, "but that number in dogs is 8,000 to 10,000." Much of COXEN's biomarker-driven cancer care is a numbers game. How does a statistical snapshot of one cancer line up with a statistical snapshot of another? Well, you need enough numbers to create crisp statistical pictures. In osteosarcoma, dogs got it and we don't. "This might allow us to learn things in dogs we can't learn in humans," says Duvall. "If we can develop new treatments in dogs, we can test them in this huge number of dogs and then transfer the knowledge to children who get osteosarcoma." But first, because of these numbers, osteosarcoma was a great jumping-off point for K9 COXEN--do the genetic signatures of the human NCI-60 predict response and resistance to K9 osteosarcoma? To find out, Duvall and her CSU collaborators Douglas Thamm, DMV, Rodney Page, DVM, and Dan Gustafson, PhD, had to make their own osteosarcoma predictions, compare them with the COXEN predictions and see if the two were copacetic. "Basically we tried to select groups of tumors that were resistant and compliant, and compare the gene signature of these two groups," Duvall says. Some dogs survived long after treatment and others didn't-- what genes made these tumors different? "By doing this we found a number of biomarkers," Duvall says. And it turns out that, sure enough, once you turn a K9 osteosarcoma into a genetic signature, its drug sensitivity is almost exactly the same as a tumor from the NCI-60 with the same signature. COULD COXEN CROSS SPECIES? I N O T H ER W OR D S , D O T H E G E N E T I C S I G N AT U R E S O F S P E C I F I C C AN C ER S T R U M P T H E D I F F ER E N C E BETWEEN HUMANS AND OUR BEST FRIENDS? Douglas Thamm, Dan Gustafson, Rodney Page and Dawn Duvall at the Colorado State University Animal Cancer Center F R O M H U MA N S TO D O G S AN D BAC K AGAI N Cancer care crosses into dogs; could it cross out? "Actually, this has a strong potential to help Theodorescu's COXEN advance faster in the human setting," says Page, director of the CSU Animal Cancer Center. "With dogs, owners and doctors, not insurance companies, decide on what treatments are given, and we don't have to wait for a drug to fail in order to try a second-line therapy. Also, it's hard to get people to accept a finding that shows a tumor is sensitive to a drug not on the standard of care list. But with dogs, you can give a promising drug not on a standard of care list and thus give Theodorescu the ammunition he needs to eventually get it put on the list." The jump back from CSU's dogs to the CU Cancer Center's patients is under way in lymphoma. "It's prevalent in both dogs and people, making it a great place to start," says Duvall. Again, it's all about the numbers game: Once Duvall gets a bead on the genetic 7 C3: SPRING 2012 GLENN ASAKAWA signature of K9 lymphoma (in the works), she'll be able to match that signature to signatures in the NCI-60 to discover which of the 110,000 tested drugs will likely work best with K9 lymphoma. Then, staying always within the bounds of compassionate care, she can test the promising drugs that COXEN picks in CSU's K9 patients. It's a short step from a dog-proven drug to humans. GLE NN ASAKAWA B I G - P HAR M AN D LITTLE D R U G S This biomarker-driven cancer care is also forcing academia and industry to step quickly out of the box of drug development mechanics it's been in since the 1950s. Sure, bigpharm is willing to pony up the $100 million needed to push a big drug through the process of FDA approval--but what about a small, targeted cancer therapy? If a drug is meant to eventually target 100 people a year as opposed to 10,000, will big-pharm still pay for it? For example, imagine if a biomarker target and a drug to nix it were found for heart cancer. Yes, it killed Eric Carr, drummer of the rock band Kiss, and yes, it's a leading candidate for Catherine of Aragon's death in 1536, but only a handful of cases are seen each year in the United States. The same is true as we split big cancers into their smaller subsets: Would big-pharm fund development of a drug to target, for example, a biomarker present in only 0.5 percent of lung cancer patients? "Personalized medicine, driven in part by matching drugs to biomarkers, is forcing industry and academia to reevaluate how we do business," says Andrew Thorburn, PhD, deputy director of the CU Cancer Center. What he means is this: don't expect bigpharm to pay for little drugs. That is, unless academia can give it to industry as a slam dunk. Thorburn says this slam dunk depends on matching drugs to biomarkers before a drug's first human trial. "If you give a targeted drug to a general cancer population, the proportion of people who respond might not be high enough to make the drug look effective," Thorburn says. In this way, drugs that could have helped the 0.5 percent die in development. The fix? Thorburn says it's in the deep science of picking apart patients' genomes for predictive biomarkers--the genes that hint at who will and who won't respond to a drug, and then testing the drug with only this high-responding population. It's a task, says Thorburn, for which academia and not necessarily industry is best suited. "That's why some cancer centers, the CU Cancer Center included, would like to put in place the infrastructure that would allow us to take a drug through phase I clinical trials in-house, in some cases before courting industry involvement," says Thorburn. "But to do so, we'll need the generosity and vision of philanthropists." The CU Cancer Center has molecular biologists on hand discovering biomarker targets, synthetic chemists making the arrows, and innovative animal researchers taking drugs to the tipping point. "What we don't have are experts who can make drugs usable for humans or the institutional money to fund clinical trials," Thorburn says. And this monkey wrench of money in the cogs of drug development mechanics means that a biomarker with potential, matched with a drug that has potential, may stay as that: potential. Currently academia can produce the frog footmen with jam-smudged lips and the Red Queen to yell "Off with his head!" In most settings, it lacks only the final axe to get the job done: money. Dan Theodorescu, MD, PhD, director of the CU Cancer Center. Learn about the CSU Animal Cancer Center www.csuanimalcancercenter.org Make a donation to support the CU Cancer Center http://giving.coloradocancercenter.org 8 WWW.COLORADOCANCERCENTER.ORG DEC DINGCANCER RECIPE FOR A BIOMARKER Ingredients: 23 chromosomes made of grade-A, organic DNA, including about 20,000 short sections known as "genes" 1 genetic mutation, either born of chance or of an environmental factor like UV exposure or smoking A pinch of messenger RNA (or just mRNA) 1 million ribosomes (give or take) Other machinery of the human body, including transfer RNA and amino acids to taste Directions: 1. Even before cooking, you might find biomarkers hidden in your first ingredient--the 23 chromosomes that make up your genome. Do you have genes that predispose you to cancer? They're biomarkers. 2. Mix genetic mutation into your 23 chromosomes and let rise overnight. Check genome again--now do you have a gene that predisposes you to cancer? Or, if you have cancer, can genetic testing determine the mutation that caused it? For example, the "translocation" of a bit of chromosome 9 into chromosome 22 known as the Philadelphia chromosome is a biomarker of chronic myeloid leukemia. 3. Add pinch of mRNA. The mRNA reads your mutated gene and transports the gene's protein blueprint outside the cell nucleus. 4. Gently fold in ribosomes. Ribosomes are ovens that cook blueprints into proteins, building proteins coded by mRNA one amino acid at a time. 5. Now not only do you have a mutation hidden in your genome, but you have the faulty protein built from this plan. Just as genes alone can be biomarkers, so too can these faulty proteins. For example, an elevated level of the protein HER2 is a biomarker for a subset of breast cancer. Mutant Gene mRNA mRNA mimics mutant gene Ribosome ovens New mutant proteins 9 C3: SPRING 2012 A CONVERSATION WITH BORSIKA RABIN, PhD, MPH, PharmD Staff Researcher and Research Coordinator for the Cancer Research Network Cancer Communication Research Center, one of five NCI-funded Centers of Excellence in Cancer Communication Research, which is housed at the Institute for Health Research at Kaiser Permanente Colorado, a CU Cancer Center consortium partner. that would be expected to die from cancer or from comorbidities in the next year, five years or ten years. These visual representations often improve patients' understanding of information. Actually, it's not only patients who benefit. We have tested the tool with 57 providers including physicians, nurses, social workers, care coordinators and other mediC3: First, could you tell us about your system? Rabin: Sure! The tool is called the Cancer Survival Query System and uses National Cancer Institute data to help healthcare providers and cancer patients understand a patient's risk of dying from their diagnosed cancer and from other existing medical conditions. C3: Don't similar online tools already exist? Rabin: Certainly--we reviewed 22 web-based prognosis applications while developing our tool. But two things make the Cancer Survival Query System unique. First, the Cancer Survival Query System has a very sophisticated way to compare a patient's chances of dying from cancer with his chances of dying from their other, existing medical conditions such as their diabetes or heart disease. C3: And second? Rabin: Second, the Cancer Survival Query System turns complicated statistics into a user-friendly visual interface--actually in a way that research shows we best understand this kind of information. Specifically, it shows a 10x10 grid of stick-figure people, so 100 people, and colors the number In the face of cancer, patients often forget about these other medical conditions and we hope that by helping patients see cancer in the context of overall health, we can encourage patients to keep taking care of their other medical needs while battling cancer. Especially with some early stage cancers, patients are more likely to die from their other medical conditions than their cancer, and we hope to help patients make the most informed treatment decisions. C3: Is this a tool you recommend patients and families use themselves, perhaps even online at home, to inform themselves and their loved ones about likely cancer outcomes? Rabin: The tool was developed with cancer specialists in mind and right now we're testing the tool with this group. Creating a more patientfriendly version might be a next stage in the life cycle of this tool. FL IKR/HAN SS CREATI VE COMMON S BY GA RT H S U N D E M One of the first questions most patients ask when diagnosed with cancer is "How does my cancer diagnosis impact my life expectancy?" Borsika Rabin, PhD, MPH, PharmD, staff researcher at the University of Colorado Cancer Center affiliate Kaiser Permanente Colorado, is testing a web-based cancer prognostic tool developed by the Statistical Research and Applications Branch of the National Cancer Institute that can help provide an accurate answer to this question. Here we talk with Dr. Rabin about her work. cal professionals--most people we could imagine being involved in care of cancer patients from four major healthcare organizations in Colorado: Kaiser Permanente, the University of Colorado Cancer Center, the Veterans Administration Hospital, and Denver Health. We received overall positive feedback with some excellent suggestions for improvement. C3: How is prognosis done now? Rabin: Most doctors make their estimates based on their experience and intuition and often using information from published studies and textbooks. The Cancer Survival Query System can help personalize these estimates by taking into account characteristics of a specific patient. C3: What interested you about this project? How did you decide to get involved with this tool? Rabin: My research area of interest is cancer communications. The Cancer Survival Query System is a great example of how to make complex and confusing data tables more accessible. This is the future of big data and I feel honored to play a small piece in this movement! The Cancer Survival Query System will help patients and doctors weigh their treatment options. 10 WWW.COLORADOCANCERCENTER.ORG The Toughest Care, The Greatest Rewards TH R O U G H H E R WO R K AT D E NVE R H EALTH AN D I N U GA N DA , O N C O LO G I ST ANA OTO N PAYS IT F O RWAR D BY LY N N C L A R K Oncologist Ana Oton knew the time had come for the cowboy. He was dying and she could do no more to help him. During his many clinic visits, Oton and the cowboy had formed a special bond, and she decided to write him a letter telling him how much she enjoyed taking care of him. "His wife called me wanting to know if I wrote that letter to everyone or just him," she recalls. "It was the first time I'd ever done anything like that, I told her. After he died, she called to thank me, to tell me how happy he was to find a doctor who really cared about him. It broke my heart." Oton earned her medical degree from the Central University of Venezuela, where students undergo a rigorous, seven-year course of study post-high school. After training, Oton moved to Spain with her parents, where she worked in a research lab. "I knew from the age of 10 that I wanted to live in the United States," says Oton, investigator at the University of Colorado Cancer Center and assistant professor of medical oncology at the CU medical school. "To do that as a physician, I had to find U.S. physicians who would write me letters of recommendation for a medical residency." For five months in 2000, Oton worked in a Miami, Fla. hospital nearly around the clock without pay in an observership, learning English on the fly. After five months, two physicians wrote her glowing recommendations and she began a residency program at the University of Miami. "I was fascinated by the type of relationships you could establish with patients," says Oton. "People were telling me their lives, trusting me. This is really powerful." Oton's winding road to Colorado included one more stop for a fellowship in oncology at the University of Pittsburgh, where she studied under lung cancer expert Dr. Chandra Belani. When her fellowship ended in 2007, she enrolled in a program that allowed her to earn her green card by working in an underserved hospital for three years. She came to Denver Health--Denver's safety net hospital and member of the CU Cancer Center consortium. "The Denver Health population is considerably underserved," she says. "About 99 percent of my patients are minority, homeless, uninsured or any combination of these. My work is very challenging because my patients not only have cancer, they have multiple problems--social problems, comorbidities--and they don't have money. Cancer is often just one problem, and it may not be as bad as other problems in their lives." At Denver Health, Oton is both doctor and social worker, offering cutting-edge clinical trials but also helping her patients get connected with needed services, and sometimes making legal statements to help bring relatives of deathly ill patients to the country to say their goodbyes. Since 2010, Oton has been involved in a series of 45-second public service announcements on Azteca, a Colorado Spanishlanguage TV network that educates viewers about cancer prevention and treatment. "We know that research should not only be applied to Caucasian patients," she says. "Hispanic groups are the fastest growing in the United States. We're talking about millions of people in the future with cancer, and we need to involve them." While Oton claims she has no spare moments in her day, she is embarking on a new project. In February 2012, she spent two and a half weeks in Uganda teaching at the University of East Africa. "In Africa, in South America, in Asian countries, you can do small things that will make a huge difference," she says. "I want to help, and to remember that people in underserved countries have exactly what I had when I was 17. It's a curiosity about life, and about people. It's a desire to help solve problems. I just want to give more to the world." Still despite growing administrative and teaching duties, it's patients like the cowboy that keep Oton connected to the meaning of cancer care. "I have been seeing patients since I was 17. I am 38. There are patients who make me smile, make me cry and make me believe in this job I do every day," she says. ABOUT ANA OTON, MD Assistant Professor of Medical Oncology, University of Colorado School of Medicine "We know that research should not only be applied to Caucasian patients. Hispanic groups are the fastest growing in the United States. We're talking about millions of people in the future with cancer, and we need to involve them." --ana oton, md 11 C3: SPRING 2012 LY NN C LARK MD CLINICAL CARE LY NN C LARK tough BY LY N N C L A R K "That dude is Tim Elliott survived hard-hitting throat cancer treatment without complaint or worry as nails" N o sore throat should last a year and a half. Tim Elliott tried antibiotics and then had an MRI. Still, doctors couldn't pinpoint what was wrong, why the condition was getting worse, why Tim lost his voice in February 2011, or why it mysteriously came back a month later. By June, Tim couldn't swallow food or water. Lacking health insurance, he went to the Salud Family Health Center in Longmont, Colo. to see a swallow specialist. That physician sent him to University of Colorado Hospital. "They called it cancer in June 2011," Tim says, sitting in his living room, sipping water. Throat cancer, to be exact. "Tim's cancer was as advanced as it gets to still be considered curable. It was located in the back of his throat and had spread to the local lymph nodes," says his oncologist, Antonio Jimeno, MD, PhD. Jimeno is a head and neck cancer specialist and laboratory scientist at the University of Colorado Cancer Center. Throat cancer is a member of a group of tumors classified as head and neck cancers, which includes cancers of the mouth, sinuses, tongue and various throat organs. Historically, these tumors have affected men (usually) who are heavy smokers and drinkers. Many head and neck cancers are survivable--two thirds of patients diagnosed will be alive three years later--but unpleasant and often disfiguring side effects frequently accompany surgery and radiation. In Tim's case, surgery would mean losing his voice box. A landmark study conducted by the Veterans Administration showed that surgery compared to chemoradiation has similar outcomes; so instead of surgery, Tim and his treatment team turned to radiation oncologist David Raben, MD, Jimeno's partner in chemoradiation. "Tim is a character," Raben says, "That dude is tough as nails. He had one of the worst tumors you could have, not just in location but in volume." Additionally, the combination of being a heavy smoker and the aggressive genetic characteristics of Tim's tumor pointed towards a poor prognosis. Tim's case was advanced and on the edge of incurable. At that late stage, instead of simply blasting the tumor with traditional radiation, which would add significant acute toxicity, Raben and Jimeno thought Tim's best chance was to target the tumor's basic biology. Tim would be one of the first patients in the world to try a new drug that put a stop sign in the middle of the lines of communication his tumor needed to survive. T O TA L C A N C E R C A R E By the time Tim arrived at the CU Cancer Center's clinical care partner, University of Colorado Hospital, he had dropped 40 pounds from his already slight frame. Tim was immediately fitted with a feeding tube, and a social worker helped him qualify for donated gas cards so he and his wife could afford the 64-mile round trip drive from their Frederick, Colo. home to the hospital for his 35 days of treatment. "In our head and neck cancer program, we have eight integrated teams to provide our patients with total cancer care, not just focusing on the tumor they have but also preventing late side effects that affect the long-term quality of life," Jimeno says. "Tim benefited from all of them, including nutrition services, speech rehabilitation, interventional radiology, social work, smoking cessation, and the three treating teams--medical oncology, radiation oncology, and ear, nose and throat surgery." 12 WWW.COLORADOCANCERCENTER.ORG But the most important part of being under the wing of an NCI-designated comprehensive cancer center was access to world-class clinical trials. In Tim's clinical trial, he'd be hit with an extremely aggressive course of chemotherapy and radiation, plus a little something special--a drug that had been given to humans in a single-agent study but had never been tried in combination with chemoradiation before. "Tim withstood three weekly infusions, for seven weeks, without complaining," Jimeno says. "We felt he needed all the help he could get to beat this cancer, and this exciting study seemed a shoe-in." But before going on the study, Tim had a few rules for study coordinator Morgan Pittman. "She told me where to go and I went there," he says. "The other rule: Don't explain, just do it. I can't do anything about this cancer, and I don't speak Latin or Greek. Just tell me what to do." Tim's wife, Toni, says doctors described the study to her like this: "Chemo is the right push, and radiation is the left push, and the kick down the middle is the experimental drug." Not only was the drug new to humans, but Tim Elliott was the first human enrolled on the trial. Phase I studies are not designed to cure a patient. They're meant to help researchers dial in the doses that may help future patients. TH E N EW "K ITC H E N S I N K" The study drug, CUDC-101, is being developed by Curis, Inc. The CU Cancer Center is the lead of three universities studying the drug's effects in a first-in-man clinical trial for aggressive head and neck cancer. In many of these cancers, the genetic signals EGFR and HER are broken in a way that tells cells to grow and spread without control. Another genetic target just hit the scene--HDAC--and CUDC-101 hits all three. "Cancer is complex, and our new drugs do more than one thing," Jimeno says. "If 15 biologic pathways are active in a tumor, inhibiting one is unlikely to help. This drug is the new `kitchen sink,' but one that is refined and focused." Indiscriminate or non-directed radiation is a thing of the past. New mapping and delivery methods allow the CU Cancer Center to precisely target its delivery. "We've gotten technically very elegant in delivery of radiation treatment," Raben says. "We can now give different doses of radiation in different areas so we can spare the muscles that allow you to swallow, spare structures related to hearing, and the glands that provide 70 percent of your mouth wetness." Raben notes that while many hospitals can purchase a $1 million radiation machine, what counts is having experts who can draw the tumor properly and deliver dosing appropriately. He and Jimeno say in terms of side effects, Tim looks today like former patients look five years after treatment. "We have real expertise in this area," he says. "We have a multidisciplinary tumor panel that's staffed by physicians who sit on national committees. We have some of the best clinical experts and the best research scientists in this cancer type. We're interested in setting the standard of care, not just following it." LYNN CLARK Above: Tim and Toni have led scouting troops for years. Right: Tim and Toni with two of their children, Daniel and KaDee. Do you have an inspirational story? Tell your story at http://story.coloradocancercenter.org. LY NN CLARK 13 C3: SPRING 2012 Tim sees it a little differently: "Everybody says I went through it good, but if that's good then I don't want to go through it bad," he says. Within two weeks, Tim could swallow water and soft foods again. Since the age of 13, Tim had been a smoker, but with the help of the hospital's smoking cessation clinic, he stopped. He thought he would lose his hair during treatment so he let his kids dye it like a snow cone. Christopher, 23, Daniel, 17, and KaDee, 13, picked a rainbow of colors--but his hair didn't fall out. The color stayed in until his next haircut. Over time, his tumor melted away. A HAPPY AND POSITIVE FUTURE Jimeno calls Toni--Tim's personal nurse, counselor and shoulder --one of the best caregivers he's ever seen. She's reluctant to take credit. "It was hard at first accepting the fact that he might not be around anymore," she says. "But his outlook the whole time was so positive that it brought me around. I was able to feed off that positivity. We both knew it was in God's hands and the doctor's hands." Jimeno and Raben concede they don't know what Tim's future will hold. Nearly a year out from his diagnosis, Tim's latest PET scan shows no evidence of active disease, which is a positive sign for hypopharyngeal cancers like his. These are considered the worst actors in the head and neck cancer theater. "We'll need a couple of years behind him before we know for sure," Jimeno says. David Raben, MD, CU Cancer Center investigator and radiation oncologist at University of Colorado Hospital. In the meantime, Tim's looking forward to getting back to Boy Scout Camp at Camp Patia with son Daniel, who will be an Eagle Scout. Scouting has been a big part of his family's life, with Toni and Tim helping to lead troops. He would also like to get back to work as a carpet layer, but still gets easily fatigued. Instead, he putters in his yard and attends physical therapy, trying to get stronger. "Is cancer a big change? Yeah," he says. "My ears still ring from the radiation. One vocal cord may not come on line. But happiness is a choice. You can't depend on circumstances to make you happy. I'm not the only person in the world to get cancer. Life goes on." And for however long it goes, Tim will live it. LYNN CLARK onthe HPV-positive head and neck cancer is rise Traditionally a disease of old men with a long history of smoking and drinking, new cases of head and neck cancer are on the rise due to the same virus that causes cervical cancer in women. Antonio Jimeno, MD, PhD, director of the CU Cancer Center head and neck medical oncology program, says about 50 percent of patients diagnosed with the disease in the United States today are HPV (human papilloma virus) positive. For outcomes, that could be good news because these cancers tend to be easily treated. However, Jimeno and radiation oncologist David Raben, MD, say it would be better to prevent the disease entirely. It's estimated that more than 80 percent of U.S. adults carry one or more strains of the HPV virus, but transmission can be stopped if girls and boys are vaccinated before their first sexual experience. "We believe that all boys and girls should be vaccinated against HPV when they are in their early teens," says Raben, whose teenage sons have been vaccinated. "Not only are you preventing a disease that can cause lifelong problems for people, you are preventing cancer." --Lynn Clark Antonio Jimeno, MD, PhD 14 WWW.COLORADOCANCERCENTER.ORG LY NN C LARK BY K I M C H R I SCA D E N Battle of the BULGE A BALAN C IN G AC T: APPLES VERSUS PEARS SKIP O' DONNE LL/ iST OC KPH OT O. C OM Tips the Scales on Cancer War 42 43 UNIVERSITY OF COLORADO CANCER CENTER RESEARCHERS LINK EXTRA FAT AROUND THE WAIST TO INCREASED CANCER RISK AND DEATH 49 50 A mericans overwhelmingly rank cancer as their No. 1 health concern, far outstripping concerns about obesity. But it turns out that rather than independent health concerns, the conditions are linked. Worried about cancer? Take care of your weight, say University of Colorado Cancer Center researchers. According to the American Institute for Cancer Research (AICR), every year an estimated 110,000 cancer deaths in the U.S. can be attributed to obesity, making it the second leading cause of cancer deaths, behind smoking. Besides raising the risk of dying from cancer, obesity also elevates the risk of developing cancer. Seven types of cancer are strongly associated with obesity: endometrial, esophageal, pancreatic, kidney, gallbladder, breast and colorectal. One U.S. study, using National Cancer Institute Surveillance, Epidemiology, and End Results data, estimated that in 2007 nearly four percent of new cancer cases in men and seven percent in women were due to obesity. While cancer percentages due to obesity varied widely by cancer type, endometrial cancer and esophageal adenocarcinoma were the highest. Colorado's obesity rate may be the lowest in the country, but even here the rate is climbing and at an alarming rate. From 1995 to 2008, Colorado's obesity rate climbed 89 percent, while the number of obese adults nationwide rose 67 percent, according to the Colorado Department of Public Health and Environment. "Everyone in Colorado likes to brag that we're the thinnest state," says Ann Thor, MD, CU Cancer Center investigator. "But it's cause for concern that the state's rate is growing faster than the rest of the country. At this rate, we're going to continue to see jumps in obesity's comorbidities�heart disease, diabetes and cancer." All fat isn't created equal. Subcutaneous fat, which lies directly under the skin and is found on the upper arms, buttocks, hips and thighs, is the body's protective wrap and energy store. Visceral fat found deeper in the body cushions the body's vital organs and contributes to belly bulge. It's this bulge that equals poorer health, says Thor. "We're starting to look more at a person's body fat distribution," Thor says, "and the central fat around a person's abdomen, or an apple-shaped body, appears to be particularly troublesome." While eating an apple a day keeps the doctor away, looking like one predicts cancer risk. Conversely, pear people (who collect fat in their hips and thighs) have lower risk despite equal overall rates of fat. To be considered healthy, waist measurements should be under 40 inches for males and under 35 inches for females. Anything above that equals higher cancer risk. "Really it comes down to does a person store their extra fat above the waist or below the waist," says Paul MacLean, PhD, CU Cancer Center investigator. Researchers also take into account body mass index (BMI) or a person's weight-to-height ratio when understanding obesity. A BMI of 18.5 to 24.9 is generally regarded as healthy or normal. At more than 25, a person is considered overweight; more than 30, they're obese. However, BMI doesn't take into account a person's waist measurement. A person can be labeled obese according to BMI, but healthy according to waist measurement. "Essentially, it's all about where the fat is gained and when the fat is gained," Thor says. 15 C3: SPRING 2012 51 52 53 54 55 56 51 57 58 FAT ' S AT TA CK O N AG E If you thought fat's greatest assault was on how others perceive your bikini body, think again. It may be on the inside and not on the outside that fat does the most damage. Scientists have found that fat cells around the waist boost the body's production of hormones such as estrogen, insulin and insulin-like growth factor 1--all of which cause cells to divide more rapidly. Fat also produces a variety of proteins that cause chronic inflammation, supporting cell growth. Both are characteristics of cancer. In women, lifetime exposure to estrogen can positively or negatively impact their risk of developing hormone-associated cancers: breast, ovarian and endometrial. Early menarche, late menopause and not bearing children all increase a woman's exposure to estrogen, and correlate with increased cancer risk. Coupled with post-menopausal weight gain, overweight or obese women have a higher incidence of breast cancer since cancer cells are fueled by glucose. The more glucose the body has, the more fuel cancer cells have to aid their growth and dispersal. "Even if a woman is not overweight or obese prior to menopause, the average woman gains 20 pounds post-menopause; and it's usually within the first few years," says MacLean. "It's this rapid weight gain that we're concerned about." MacLean and other CU Cancer Center researchers believe if they can identify the peri-menopausal window, they can potentially reduce glucose levels, rapid weight gain and elevated estrogen levels in women. "If we can find the window where everything comes together, it may be possible to develop prevention and treatment strategies that specifically target the risk window of menopause," says Pepper Schedin, PhD, investigator and co-director of the Young Women's Breast Cancer Translational Program at the CU Cancer Center. FAT, RATS AN D A BIG WIN D OW In 2005, Schedin wanted to learn more about obesity and its potential impact on breast cancer. She was introduced to MacLean, an expert in obesity and nutrition. The two joined forces to apply for a CU Cancer Center seed grant to study whether obesity promoted post-menopausal breast cancer. 100,500 CAN C E R CAS E S P E R YEAR AR E L I N K E D T O E X C E S S B O D Y F AT OBESITY-LINKED CANCERS The American Institute for Cancer Research lists these cancers as linked to excess body fat. 100,500 CASES PER YEAR 49% of endometrial cancers = 20,700 cases/year 35% of esophageal cancers = 5,800 cases/year 28% of pancreatic cancers = 11,900 cases/year 24% of kidney cancers = 13,900 cases/year 21% of gallbladder cancers = 2,000 cases/year 17% of breast cancers = 33,000 cases/year 9% of colorectal cancers = 13,200 cases/year The grant allowed them to make fat rats. The team started off with two groups of rats: lean and obese. Both groups underwent surgical ovarectomy, were fed high-fat, "western diets" and had prior tumors. Regardless of whether the rats were lean or obese, both groups gained a lot of weight, says MacLean. "The obese rats had more tumors that progressed and less that regressed." MacLean says. "No matter how you look at it, the obese rats came out of ovarectomy with more tumor burden and incidence." But the research team wanted to take it to the next level. Schedin and MacLean recruited two more CU Cancer Center investigators: Steve Anderson, PhD, an expert in breast cancer molecular biology, metabolism and glucose utilization; and Thor, an expert in dietary factors and hormones. The four became the "Fat Rat Group." Looking back on data, the team was surprised by the short period of time it took the rats to gain the weight--all during the three weeks post ovarectomy. This spurred the team to consider interventions that could be utilized prior to high-risk women hitting menopause. "In normal women the menopausal transition can vary from one to several years, or it can be very quick if a woman has a hysterectomy for other health-related reasons," says Schedin. "That's a big window to target. But, if we can find high-risk women, who may have a family history of breast cancer, prior to menopause, we may be able to alter their future health outcomes." M ETFORM IN : A H ISTORIC A L WON DE R In 2008, the `Fat Rat Group' was awarded a three-year, $600,000 grant from the Susan G. Komen for the Cure Foundation to try a drug on their fat rats--a common diabetes drug called metformin, which Thor had found killed breast cancer cells. Knowing that the body's tissues "don't clear glucose fast enough" in the obese condition, Anderson says that clearing glucose may be an opportunity to improve metabolic regulation in post-menopausal women. This is where the wonder drug metformin comes in. "In our current study, we want to show that metformin stabilizes blood glucose levels, stops the breast cancer tumors from growing and improves overall metabolic function," Anderson says. P E R CE NTA GE 16 WWW.COLORADOCANCERCENTER.ORG 59 60 61 62 63 64 65 LISA LIT ZE NBE RGE R 66 67 The CU Cancer Center Fat Rat Group meets weekly to discuss research findings and funding opportunities. While metformin has been around since the mid-1900s, it's just begun to be studied in epithelial cancers--breast, lung, colon and prostate. Data suggests that metformin reduces breast cancer cells' addiction to sugar, inhibits tumor growth, and induces cell death--making this inexpensive, easy to come by and low-toxicity drug exciting, says Thor. "Metformin has the possibility of preventing cancer," Thor says. In the long run, Thor believes metformin will reduce the incidence of breast cancer in patients with diabetes, but she believes physical activity and diet should be part of the equation. D RO P P I NG T HE FAT, I MPR O V I NG T HE O U T CO M ES The NCI estimates that one-third of cancers can be prevented through diet, physical activity and weight management. However, researchers haven't discovered the magic number of pounds it takes to reduce cancer risk. At the CU Cancer Center, cancer prevention and control experts Tim Byers, MD, MPH, and Rebecca Sedjo, PhD, are conducting an new trial called Exercise and Nutrition to Enhance Recovery and Good Health for You (ENERGY)--an NCI-funded study looking at the effects of weight loss on quality of life and eventually cancer recurrence in breast cancer survivors. Four cancer centers are following 800 participants over the course of two years. "Typically if breast cancer survivors are heavier they have worse outcomes for recurrence and mortality," Sedjo says. Looking to lose weight? The new Anschutz Center for Health and Wellness may have the program for you. www.coloradocenter.com "Right now, we think that weight loss can change those outcomes but there is no population data. This study will be the first to really help answer that question." While researchers can't conduct clinical trials requiring people to gain weight, they can help people lose it. Preliminary studies suggest that even modest levels of weight loss among the obese may reduce cancer risk. The ENERGY trial is encouraging participants to lose seven percent of their body weight--a number that has shown to reduce the risk of diabetes and poor cardiovascular health. But researchers know that weight loss isn't easy. One way to encourage weight loss is to connect dieters with a support group of like-minded dieters, and so the ENERGY trial is designed to build an instant support group. "The great thing about the ENERGY trial is all of the participants are breast cancer survivors, all of them are overweight, and all of them are women creating an ideal support system needed for weight loss," Sedjo says. Only time will tell if the ENERGY trial produces the results necessary to improve cancer outcomes. In the meantime, CU Cancer Center researchers like Thor, MacLean, Anderson, Schedin, Byers and Sedjo will continue building the connections between obesity and cancer, and convincing people that `pears' are better than `apples.' "Here at the CU Cancer Center, we're really in an ideal position," MacLean says. "We have cancer and metabolic researchers who are all interested in understanding the relationship between obesity and cancer, coming together under one roof." "And instead of waiting until people get cancer and then treating it, we're figuring out ways to prevent it," adds Thor. 17 C3: SPRING 2012 S U P P O R T E R F CUS C OURT E SY OF T H E MORGAN ADAMS FOUNDAT ION Unconditional Love TH E MORGAN ADAM S FOU N DATION DR IVE S CR EATIVITY AN D EXPLORATION I N PE DIATR IC CANCE R R E S EARCH BY K I M C H R I SCA D E N Morgan Adams was a typical 5-year-old girl. She loved the color pink, fairies, chocolate cake and dressing up in princess clothes. She loved pasta, her little brother and hiccups. But most of all she simply loved, unconditionally. In December 1997, Morgan's life changed forever. She was diagnosed with glioblastoma multiforme, an aggressive malignant brain tumor rarely seen in children. She needed emergency surgery. After a successful surgery at Children's Hospital Colorado, Morgan endured 11 months of additional treatments, celebrating many "wins" along the way. Yet the tumor relapsed. With no treatment options left, Morgan passed away in November 1998, four months after her sixth birthday. Two years later Morgan's parents Joan Slaughter and Steven Adams wanted to give back. They decided to join the Oncology Advisory Board at Children's Hospital Colorado, the University of Colorado Cancer Center's pediatric patient care partner. "Through our conversations with many of Morgan's oncologists, we kept hearing over and over again that pediatric cancer research was seriously underfunded," Joan says. "When we started to learn more about this need, we wanted to find a way to help." Driven by Morgan's unconditional love, in February 2001 Joan, Steven, and a handful of close family and friends hosted a small local art auction called ARTMA, or "Art for Morgan Adams." Out of ARTMA's success came the creation of a second event, the Morgan Adams Concours d'Elegance, a rare automobile and aircraft show. For the first few years, Joan and Steven ran the two events through the Children's Hospital Colorado Foundation. In 2003, Joan and Steven were asked to fund a pediatric glioblastoma multiforme study that had shown promise in adults. However, the principal investigator was in New York, not at Children's. Because the research data was to be shared with Children's, Joan and Steven decided to fund it. "This started our interest in collaborative research studies and multi-site studies," Joan says. "But in order to fund those we needed to be independent of Children's." That year, Joan and Steven founded The Morgan Adams Foundation, which is dedicated to funding laboratory and clinical research in the area of pediatric cancer, specifically cancers of the brain and spine. "Our interest is in increasing survival rates and reducing the devastating side effects of treatments," Joan says. "In order to do that, we need to invest in drug development and innovative approaches to treating pediatric patients." Since 2003, The Morgan Adams Foundation has given more than $1.75 million in seed and bridge grants for viable investigations not yet ripe enough for funding by large organizations. CU Cancer Center investigators Nicholas Foreman, MD; Lia Gore, MD; Arthur Liu, MD, PhD; Sarah Rush, MD; and Rajeev Vibhakar, MD, PhD, have received awards over the years. This year, the foundation awarded two grants to Liu and Foreman. Liu was awarded $20,000 to research structural and genetic predicators of neurocognitive deficits in children with brain tumors. Foreman was awarded $30,000 to study the genetic abnormality known as a BRAF mutation, in atypical teratod rhabdoid tumors, a rare pediatric brain tumor. Prior to funding from The Morgan Adams Foundation, the pediatric neuro-oncology research program at Children's only comprised Foreman and one other researcher. Today, the team comprises 14 people dedicated to researching pediatric The Morgan Adams Foundation morganadamsfoundation.org The Morgan Adams Foundation hosts four annual or biannual fundraising events: ARTMA, The Morgan Adams Concours d'Elegance, the Race Against Kids Cancer and Friday Night Fights. This year the foundation will host its tenth Concours d'Elegance on August 25 at Centennial Airport. COURTESY OF T H E MORGAN ADAMS FOUNDAT ION Left: Steven Adams and Joan Slaughter, founders of The Morgan Adams Foundation at ARTMA 2012 Above: Morgan Adams, age 6, at the start of first grade. "The pediatric neuro-oncology research program is one of the strongest in the country and would have literally not existed without the funding from The Morgan Adams Foundation," Foreman says. The majority of The Morgan Adams Foundation funding stays with researchers in Colorado. If there are out-of-state studies or clinical trials that can directly benefit patients in Colorado, the foundation will consider funding if they collaborate with Colorado researchers. "Colorado is very lucky to have the brain trust that we do," Joan says. "We've been amazed by how dedicated all the researchers and clinicians with whom we work are--and how incredibly well they all work together." Foreman says, "There are literally children alive now, survivors from brain tumors, who would have died without the research funded by The Morgan Adams Foundation." 18 WWW.COLORADOCANCERCENTER.ORG brain tumors. C O M M U N I T Y N E W S S AV E T H E D A T E AUGUST 4 � DINNER IN WHITE Join AMC Cancer Fund on Aug. 4, 2012 for one of Denver's hottest and most creative fundraising events--the 3rd annual Dinner in White. Modeled after the Diner en Blanc in Paris, Dinner in White delivers an evening under the stars with music, cocktails and Parisian desserts. Unlike other fundraising events, guests are kept in suspense about where the event will take place until an hour before when a text message is sent out revealing the location. Once notified, guests dressed in white are treated to Paris in their own backyard. Tickets are $50 and can be purchased at www.dinnerinwhite.com. BREAST CANCER RESEARCH PROGRAM RECEIVES $100,000 FROM KAY YOW CANCER FUND, THE V FOUNDATION Research on breast cancer after pregnancy at the University of Colorado Cancer Center is reaching a key milestone thanks to a gift from NCAA women's basketball charities. The Kay Yow Cancer Fund and The V Foundation for Cancer Research annually fund cancer research First Dress in Blue Day event spotlights colorectal cancer The Cancer Center's Colorado Colorectal Screening Program hosted its first Dress in Blue Day on March 2, 2012 at Tocabe, an American Indian eatery in Denver. The event raised more than $600 and five local physicians donated 109 colorectal screens, allowing the program to screen more uninsured Coloradans. CLIFF WORKMAN based in the host city of the NCAA Women's Final Four. This year, the $100,000 grant will fund continuing work at the CU Cancer Center aimed at preventing young women's breast cancer. "We're at the point where this money will help us finalize the data "This money will help us Borges, MD, MMSc, a CU Cancer Center investigator and co-director finalize the data we need of the center's Young Women's Breast Cancer Translational Program. to support a clinical trial. " Marsha Sharp, executive director of the Kay Yow/WBCA Cancer --virginia borges, Fund, and Nick Valvano, CEO of the V Foundation for Cancer Research, md, mmsc presented Borges and Pepper Schedin, PhD, co-director of the we need to support a clinical trial for the prevention of postpartum, pregnancy-associated breast cancers," says grant recipient Virginia program, with a ceremonial check on Dec. 1, 2011. "It is so encouraging to fund research whose target is not only the treatment of breast cancer, but the prevention as well," says Valvano. "We are proud to be associated with this project." Founded in 2005 by Borges and Schedin, the Young Women's Breast Cancer Translational Program specializes in the treatment and prevention of breast cancer in women under age 40, with a special focus on pregnancy-associated breast cancer. The program provides treatment and support to more than 100 women each year. "Dr. Schedin and I are the right arm and the left arm of this research organization, and so this grant from the Kay Yow and Jimmy V Foundations will directly fund research that benefits young women," Borges says. BRIDG ET FOSSED AL ANIMAL CANCER CENTER APPOINTS NEW FACULTY THANKS TO GIFT FROM ANSCHUTZ FOUNDATION With support from the Anschutz Family Foundation, the Animal Cancer Center at Colorado State University named Jenna Burton, DVM, DACVIM, the first full-time clinical trials faculty member. "We are extremely grateful to the Anschutz Foundation for this support," says Rodney Page, DVM, DACVIM, director of the CSU Animal Cancer Center and CU Cancer Center investigator. "This funding strengthens our mission and sustains our partnership with the University of Colorado Cancer Center to better understand the connection between cancer in pets and cancer in people as a critical tool for Cocktails for a Cure raises $160,000 for women's cancer research Cocktails for a Cure, AMC Cancer Fund's annual women's event, raised $160,000 for women's cancer research. Nearly 300 attendees sipped on signature cocktails, bid during the live auction and listened to a survivor's story. cancer control in all species." The CSU Animal Cancer Center's clinical trials program conducts investigations of new drugs, treatments and procedures for cancer in companion animals. Results of these trials have contributed to major advances in translational research, bridging the gap in bench-to-bedside therapies for animal and human cancer patients. "This position will serve a critical role in translating the scientific findings in pet animals to human cancer, and so provide information that will help cancer patients of all species," says Dan Theodorescu, MD, PhD, director of the CU Cancer Center. DAN W E AVE R 19 C3: SPRING 2012 UNIVERSITY OF COLORADO DENVER SPRI NG 2012 www.coloradocancercenter.org 13001 EAST 17TH PLACE, MSF434 AURORA, CO 80045-0511 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, Lynn Clark Photos: Lynn Clark, Glenn Asakawa, Casey Cass, Lisa Litzenberger, Cliff Workman, Bridget Fossedal 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. Anschutz Cancer Pavilion Expansion Opens May 2012 W LYNN CLARK hen the Anschutz Cancer Pavilion at University of Colorado Hospital first opened in 2000, the University of Colorado Cancer Center saw nearly 44,000 patients a year. Now, it's at 110,000 patient visits per year, with no sign of slowing. In May, the Cancer Center will open a five-story addition to the Anschutz Cancer Pavilion expanding the space to include: 40,800 square feet of new space 14,100 square feet of renovations 18 new chemotherapy infusion bays 33 additional patient rooms A new treatment vault for expanded radiation therapy In total, the expansion will enable the Cancer Center to treat 60 percent more cancer patients every year. 20 WWW.COLORADOCANCERCENTER.ORG M ULTIV ISTA CAS EY CASS