C3: Collaborating to Conquer Cancer Spring 2013
The University of Colorado Cancer Center's spring 2013 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 SPRI NG 2013 Stop Signals BREAKING CANCER’S CELL SIGNALING 12: PRESERVING OPTIONS 16: CONNECTING THE DOTS 10: Q&A WITH RAJESH AGARWAL, PhD 11: C3 MD JANA BOLDUAN LOMAX, PsyD 18: SUPPORTER FOCUS ON ROCKY MOUNTAIN ITALIAN GOLF ASSOCIATION ANSCHUTZ MEDICAL CAMPUS SALPINGECTOMY AN EVOLVING OPTION FOR YOUNG WOMEN AT RISK FOR GYNECOLOGIC CANCERS In women at risk for ovarian cancer, the common prevention strategy is to remove fallopian tubes and ovaries as soon as the woman has stopped having children. However, this may initiate side effects associated with menopause. A CU Cancer Center study suggests a way young women can reduce their risk while leaving menopause for later: salpingectomy—a technique that removes the fallopian tubes while leaving ovaries intact. “Within the last five years, we’ve come to understand that most genetic ‘ovarian cancers’ actually start in the fallopian tubes and so removing these tubes appears to greatly reduce risk,” says Monique Spillman, MD, PhD, associate professor of gynecologic oncology at CU School of Medicine. Spillman is quick to point out that proving the effectiveness of the technique in SPILLMAN N3WS I N T E R N AT I O N A L A G R E E M E N T C O U L D L E A D TO M O R E , GOOD SCIENCE CU Cancer Center has entered its first international agreement with National Taiwan University College of Medicine. The agreement includes the promotion of collaborative research and exchange of faculty members, students, research outcomes and publications. “Globalization is important in cancer research,” says Fred R. Hirsch, MD, PhD, associate director of CU Cancer Center’s international program. “Working with other countries may give us a better understanding of cancer and whether reducing risk will require further study. A national multi-site clinical trial is planned and will start soon. Until then, Spillman considers salpingectomy an option for high-risk women below 40 who stopped having children, and are uncomfortable with the current standard of care. LONG-TERM SIDE-EFFECTS OF NEW, TARGETED THERAPIES IN PEDIATRIC CANCER PATIENTS While pediatric oncologists expect traditional side effects of chemotherapy—low white blood count, infections and infertility—they don’t necessarily expect new treatments to be equally toxic. But, researchers are learning they need to look for different side effects. “Until we have more information about the long-term effects of these therapies in children, we need to be careful about how and when we prescribe them,” says Chris Porter, MD, assistant professor of pediatrics at CU School of Medicine. Researchers know that molecularly targeted therapies may stunt the growth of pediatric patients, delay puberty or speed the onset of diabetes, but they’re just starting to explore the unforeseen side effects, such as neurocognitive, balance and motor defects. “The message I really want to convey is that our way of treating pediatric cancer has changed entirely in some diseases, and in some it’s meant huge progress. A number of us have patients who have literally been cured by these new drugs,” says Lia Gore, MD, associate professor of pediatrics and medical oncology at CU School of Medicine. “The question is how do we best treat these kids, knowing that cancer remains the enemy?” Until these questions are answered, researchers recommend using molecularly targeted therapies with pediatric patients only in the context of a clinical trial. it appears differently in different countries and regions of the world and whether it may be based on ethnicity.” For example, in the U.S. approximately 10 percent of lung cancer patients have tumors with the EGFR mutation. In Asia, between 40-50 percent of patients have the mutation. This new partnership may help researchers discover why. CU Cancer Center Director Dan Theodorescu, MD, PhD, also believes the partnership will be good for patients worldwide because each side can draw on the other’s expertise and resources. “We can learn from each other. And the collaboration could lead to faster completion and more efficient conduct of clinical trials that could more quickly lead to new cancer therapies,” he says. FL ICK R: CREATIV E COMM ONS HEALTHY LIFESTYLE DURING MENOPAUSE MAY DECREASE BREAST CANCER RISK LATER ON Obese, postmenopausal women are at greater risk for developing breast cancer and their cancers tend to be more aggressive than those in lean counterparts. CU Cancer Center researchers tracked where the body stored extra fat and sugar. “In lean models, excess fat and glucose were taken up by the liver, mammary and skeletal tissues. In obese models, excess fat and glucose were taken up by tumors, fueling their growth,” says Erin Giles, PhD, postdoctoral researcher and the paper’s lead author. In short, if you are lean, excess calories go to healthy tissue. If you are obese, excess calories feed the tumor. It turns out the menopausal window may be an opportunity for women to control their breast cancer risk, especially those who are obese when they enter menopause. Together, the study’s results suggest that the combination of obesity and weight gain during menopause can impact breast cancer in two ways. First, tumors that arise in obese women appear to have a metabolic advantage, and second, the inability to store excess calories in healthy tissues may further fuel tumor growth. “While drugs may be useful in controlling breast cancer risk in obese, postmenopausal women, our results imply that a combination of diet and exercise may be equally, if not, more beneficial,” Giles says. 2 WWW.COLORADOCANCERCENTER.ORG THE CURRENT STATE OF LUNG CANCER TREATMENT Paul Bunn Jr., MD, CU Cancer Center investigator and executive director of IASLC, says we’re in a new era of lung cancer treatment. Oncologists have shifted from blan keting lung cancer with radiation and chemotherapy to targeting the BUN N specific genetic mutations that cause lung cancer’s many varieties. The first of these oncogenic lung cancer mutations to be exploited by a drug was the epidermal growth factor receptor (EGFR), described in 2004 and targeted by the drugs erlotinib and gefitinib. Then in 2007, the oncogenic ALK/EML4 fusion protein was described and is now targeted by the drug crizotinib. “Pathologists used to define lung cancer as one of four types, based on its appearance,” Bunn says, “but it’s much more heterogenous than that. Some of these driver mutations may only be present in 1 or 2 percent of the lung cancer population, and mutations in combination may make for hundreds of species of the disease, each with its own response characteristics to targeted drugs and drug combinations.” Bunn points out that in the lung cancer varieties whose driver oncogenes can be matched with tar geted therapy, we tend to see 70-80 percent patient response as opposed to 20-30 percent response to traditional chemotherapies, and with much reduced side effects. But with this great promise of picking off cancer varieties one by one according to their oncogenes comes the challenge of testing drugs that are effective in perhaps only one of every 100 lung cancer patients. The challenge is twofold: enrolling enough patients on a clinical trial to make the results meaningful and securing funding for a trial in which the drug will only be marketable to a small slice of the lung cancer population. In addition to therapies targeting oncogenes, Bunn says Phase III clinical trials of lung cancer vaccines are currently in development. These vaccines will aid the body’s immune response against the cancer and search for ways to promote the function of tumor-suppressor genes. Overall, novel lung cancer treatment options are exploding. In the future, most lung cancer patients with a variety of genetic mutations can expect to be treated with new targeted therapies. SPARC REDUCES INFLAMMATION, THUS BLADDER CANCER DEVELOPMENT AND METASTASIS Cancer researchers are increasingly aware that in addition to genetic mutations in a cancer itself, characteristics of the surrounding tissue can promote or suppress tumor growth. One of these important tissue characteristics is inflammation because cancers prosper in and attach to inflamed tissue. A study by CU Cancer Center Director Dan Theodorescu, MD, PhD, shows that the protein SPARC acts much like an anti-inflammatory drug, attempting to heal tissues inflamed by tumors. Bladder cancer has developed ways to turn off the production of SPARC, thus allowing growth and metastasis, especially to the lung where bladder cancer is frequently fatal. “In fact, we show the effects of SPARC go beyond even this anti-inflammatory role. Additionally, the protein is involved in disallowing migrating cancer cells from attaching at possible metastasis sites and stopping the production of new blood vessels needed to feed tumor tissue,” Theodorescu says. “We hope this provides the rational basis for further exploring manipulation of SPARC as a therapeutic intervention.” LONGER LIFE EXPECTANCY NECESSITATES NEW STRATEGIES The population of the United States is getting older, which means an increase in the diagnosis of prostate cancer, often at more aggressive states that don’t respond to traditional treatments. CU Cancer Center members reviewed the modern state of prostate cancer care, examining not only new drugs but entirely new classes of drugs that may be effective and well tolerated in these aging patients. “For patients with advanced prostate cancer, there are more options than ever before,” says Elizabeth Kessler, MD, oncology fellow and the review’s lead author. “But with more options comes a more complex decision tree in choosing appropriate therapies.” First among these options are targeted therapies that are able to selectively kill cancer cells with fewer side effects than traditional chemotherapies. “Drugs like abiraterone and enzalutamide that have been approved for use in late stage prostate cancer are now being evaluated for earlier use,” Kessler says (see page 4 for article on androgen-driven cancers). Another promising strategy to treat metastatic prostate cancer is immunotherapy. In immunotherapy, treatments are used to sensitize the body’s immune system to attack cancer cells. For example, the drug Sipuleucel-T was approved by the FDA in 2010 for treatment of metastatic prostate cancer; however, “it requires blood to be removed, treated and reinfused,” says Kessler—a procedure that can only be accomplished at specialized centers. Other immunotherapies including Prostvac are in development or clinical trials, including an open trial at CU Cancer Center. Finally, researchers are exploring ultra-precise targeting of radiation and specialized drugs to attach to bone metastases. “One of these drugs is alpharadin,” Kessler says, “which goes only shallowly into bone Get more CU Cancer Center news on our blog: www.coloradocancerblogs.org Sign up for our bimonthly newsletter, Colorado Cancer News. and so targets lesions without stopping the production of bone marrow.” “There has been a major shift in the acceptance of these drugs,” she says. “We’re learning to reach for them sooner and more frequently in place of traditional chemotherapies.” GLENN ASAKAWA FOR PROSTATE CANCER CARE 3 C3: SPRING 2013 Stop Signals Androgens, Arnold & New Targeted Treatments IN BLADDER AND BREAST CANCERS BY GA RT H S U N D E M 4 WWW.COLORADOCANCERCENTER.ORG T H INKST OC K W Have you seen early Arnold Schwarzenegger movies like “Platoon” or “Conan the Barbarian?” While they’re not necessarily groundbreaking cinematic achievements, these movies do a spectacular job of one thing: showing the power of hormone growth signaling. hat—did you think Conan was just naturally barbaric? Not so much. Instead, in addition to beefy genes and the growth signals of pumping iron, the former Mr. Universe supplied his muscles with then-legal anabolic-androgenic steroids that told his biceps to bulge and his triceps to take on the appearance of well-bred pygmy rhinos. See, most of the 100 trillion or so cells that make up the adult human body spend much of their lives sitting around in lattices like inert little egg carton divots, forming the somewhat static structure and functions of your body. They sit like this until they’re told to grow, divide and proliferate. In males, the androgen known as testosterone tells cells to grow. The testes produce the bulk of it; it floats around in the blood; cells with the right receptors detect and gather it; and then these signaled cells react by turning on the their genetic growth machinery. Unfortunately, in addition to the cells of the former California Governor’s musculature, there are cells in our body we would rather didn’t grow, namely cancer cells. And sometimes these cells have hijacked the same machinery—sometimes these cells have mutated to become so super-sensitive to androgen that even the body’s natural production creates signals that lead to the haywire growth of cancer. Now researchers at CU Cancer Center are discovering more about how androgens drive diseases such as breast and bladder cancers—diseases for which pioneering work at CU first showed androgen’s role. These discoveries from deep in the labs of our member institutions are allowing doctors in University of Colorado Health system clinics to target cancer’s dependence on androgen signaling in first round clinical trials. Knowing the cause of cancer’s growth allows doctors to target its demise. BRE NDA GOT T SABE ND IN ORDER TO ADAPT, CELLS NEED MESSAGES FROM THE OUTSIDE WORLD. IN LARGE PART, THESE MESSAGES COME IN THE FORM OF HORMONES. Most humans have two arms, not four. We have ears but not horns, fingernails but not claws, and brains big enough to produce at least partial understanding of particle physics and Lady Gaga. This is because over many millennia we’ve adapted to our surroundings. Survival is an equation that balances the energy we consume against the energy we spend, and so your body has evolved to grow and maintain only the structures it needs. But this means the body’s cells need to know their surroundings. In order to adapt, they need messages from the outside world. In large part, these messages come in the form of hormones. For example, when a cougar jumps from a tree into the trail in front of you, your body produces the hormone ANDROGEN GROWTH SIGNALING adrenaline. Your cells recognize this adrenaline signal and your lungs speed up, your blood vessels dilate to carry more nutrients, and you scream like the heroine of a zombie movie. Cells’ sensitivity to their surroundings also has longer-term consequences. For example, a Northwestern University study found that the more hours per day a dad spends with his kids, the less testosterone he produces. The experience of fatherhood suppresses the production of testosterone in men by an average of 30 percent, leading to both decreased muscle building and a lower chance that fathers will eat their young (though we all know some days we’re tempted). As previewed, some cancer cells also depend on testosterone signaling. Instead of affecting the production of testosterone, cancer cells tend to turn up the volume of growth signals produced by the testosterone that exists naturally in the body. “In many ways, a cancer cell is a caricature of a healthy cell,” says CU Cancer Center Director Dan Theodorescu, MD, PhD. Think about the caricature artists you see on Denver’s 16th 5 C3: SPRING 2013 MARLA KE OW N, A URORA SE NT INAL production. Newer treatments use drugs to blunt this production or to plug cancer cells’ androgen receptors so they can’t grab their hormone targets. This work in prostate cancer is the backdrop for current work in hormone-driven cancers, but since the early days of antiandrogens, new hormonal drivers and new ways to block them have taken center stage. Dan Theodorescu, MD, PhD, director of CU Cancer Center. CASEY CASS Jennifer Richer, PhD, associate professor of pathology, explains the role of cell signaling in breast cancer. Street Mall on a sunny summer day: They draw subjects with every feature exaggerated. Likewise, “a cancer cell is like a normal cell, just with some features exaggerated—in many cases becoming more sensitive to signals that also drive the growth of healthy cells or less inhibited by signals that suppress growth,” Theodorescu says. One way cancer cells become more sensitive to hormone signaling is by producing additional hormone receptors—hormones like testosterone float around the body but only the cells that can grab it with receptors get its message. The more receptors, the more hormone molecules the cell can grab and the more sensitive the cell is to the signal. “The cell of a hormone-driven cancer might be completely loaded with these things,” Theodorescu says. A Nobel Prize was awarded in the 50’s for the discovery that androgens and estrogens control cancer growth, most notably estrogens in breast cancer and androgens in prostate cancer. In prostate cancer, genetic mutations can make receptors super sensitive to androgen so when they grab testosterone, growth signals are grossly amplified. They’ve hijacked signals of healthy growth for their own unhealthy purposes. So the historical treatment for prostate cancer was to remove the source of testosterone About 70 percent of breast cancers are estrogen-receptor positive. (Note: estrogen, not androgen.) Rather than these cells containing molecules of estrogen as their name suggests, the label “estrogenreceptor positive” means that the cell contains receptors that grab any available estrogen. Estrogen-receptor positive breast cancer uses estrogen signaling to drive its growth. “Adult cells in general are not supposed to be dividing unless they get a cue to tell them to divide. This is something the tumor takes advantage of—receptors can mutate to become ultra-sensitive, transmitting a growth signal that’s much more powerful than it should be. Sometimes the receptors are overexpressed. Sometimes they get much better at trapping circulating hormones,” says breast cancer researcher, Jennifer Richer, PhD, associate professor of pathology and co-director of CU Cancer Center Tissue Biobanking and Processing Shared Resource. A breast cancer cell that is hypersensitive to estrogen or another growth-inducing hormone sounds like a bad thing. However, a cancer’s sensitivity can be an addiction and, for example, estrogen-positive breast cancer can be combatted by anti-estrogen therapies, such as the drug tamoxifen. Specifically, this drug splits into molecules that bind to and plug a cancer cell’s estrogen receptors, stopping the growth signal from being transmitted. With receptors plugged, ER+ breast cancer cells can’t grab estrogen and without estrogen, these hormoneaddicted cancer cells don’t grow and eventually die. Estrogen isn’t alone—the growth of breast cancers can also be driven by progesterone receptors (PR+) or the HER2 (HER2+) growth factor receptor. In all cases, a hormone or growth factor driver provides a therapeutic target—without a driver, doctors are left with “triple-negative” breast cancer that seems to grow and proliferate even without signals from these hormonal and genetic culprits. “Triple-negative is a clinical classification. It’s the way doctors treating the disease categorize it—no ER, PR or HER2—and it informs treatment decisions. But calling it triple-negative is a little misleading,” Richer says. “Something is still driving it. Saying it’s triple negative is just a way of saying we don’t know what the driver is yet.” When scientists discover a cancer’s addiction—how it drives its growth—doctors can target it. This is the model of the partnership between Richer and Anthony Elias, MD, breast cancer program director at CU Cancer Center. Richer’s lab uses cell culture and mouse models to discover and validate breast cancer ANDROGEN IN BREAST CANCER 6 WWW.COLORADOCANCERCENTER.ORG Haihua Gu, PhD, Jennifer Richer, PhD and Nicole Spoelstra analyze cell growth in a breast tissue sample at CU Cancer Center. targets and treatments. Elias incorporates those findings into clinical trials with his patients. The pair has been leading the national charge toward proving a new driver and target in breast cancer: androgen. It turns out, in many women’s breast cancers live cells that act like Conan the Barbarian. These cells have learned to drive their growth with androgen receptors. Thus, when they grab testosterone or other even more potent metabolites of testosterone, they grow like Schwarzenegger’s muscles. Overall, 77 percent of all breast cancer cells are androgenreceptor (AR) positive. And, “even 10-25 percent of triplenegative breast cancers continue to express AR,” Richer says. This means that up to 25 percent of these hardest-to-treat breast cancers could be susceptible to treatments that block cells’ androgen signaling ability–like the treatments currently in use with prostate cancer. Richer and Elias recently started a first-of-its-kind, phase I clinical trial at CU Cancer Center using the anti-androgen drug enzalutamide (approved for prostate cancer use), with advanced breast cancer patients who haven’t responded to existing therapies (clinicaltrials.gov identifier NCT01597193). “This work is a concise example of modern cancer science in action,” Elias says. “We noticed something in the clinic, namely that AR was high in breast cancers resistant to anti-estrogen therapies; worked on it in the lab, and now are happy to report the lab work is once again back in the clinic where it has the very real potential to benefit patients.” The drug works in an interesting way: Instead of stopping the body’s production of testosterone (e.g. Lupron), or blocking cells’ androgen receptors (e.g. Casodex), enzalutamide works by keeping androgen receptors from pulling their payloads inside the cell’s nucleus. “Normally, the way these hormones work is by attaching to receptors in the cell cytoplasm, at which point the receptor draws itself and the hormone molecule inside the nucleus where it regulates genes,” Richer says. The genes regulated by these hormones tell breast cancer cells to survive and reproduce beyond control. Enzalutamide makes androgen receptors unable to go into a cell’s nucleus—and so the message of uncontrolled growth never gets delivered. Richer and Elias suggest that, serendipitously, the inability of breast cancer cells to pull androgen inside their nuclei may stop them from driving their growth with estrogen signaling as well. “We’ve seen that something in this estrogen growth signaling also depends on the presence of androgen receptors,” Richer says. In their preclinical work, the anti-androgen drug enzalutamide was as effective as the anti-estrogen drug tamoxifen in reducing tumor growth in preclinical models of breast cancers that have both androgen and estrogen receptors. If this sounds like a great leap forward in the way the world treats breast cancer, that’s because it certainly may be. Richer and Elias recently earned a major grant from the U.S. Department of Defense Breast Cancer Research Program to continue their interplay of lab and clinical work that could solidify anti-androgen therapies as common arrows in the quiver of breast cancer care. “Sure, cancer cells continue to mutate. You put selective pressure in one place and they can mutate to a different dependence,” Richer says. “What we’re hoping is that when 7 C3: SPRING 2013 C ASE Y C ASS C ASE Y C ASS IN MANY BREAST CANCERS LIVE CELLS THAT ACT LIKE CONAN THE BARBARIAN: THEY DRIVE THEIR GROWTH WITH ANDROGEN RECEPTORS. WHEN THEY GRAB TESTOSTERONE, THEY GROW LIKE SCHWARZENEGGER’S MUSCLES. we combine anti-androgen therapy with something like the antiestrogen tamoxifen or aromatase inhibitors, it may kill enough of the cells that they won’t be able to mutate fast enough to keep pace—that they won’t be able to come back.” Soon breast cancer doctors may target the disease with a prostate cancer drug. But the list of cancers that may benefit from anti-androgen therapies doesn’t end with two. Now you know many ways to break the chain of androgendependent growth signaling: by stopping hormone production, by blocking the attachment of hormone to receptor, or by keeping the receptor from pulling its payload inside the cell nucleus. Similarly, there are many links in the chain that connects the occurrence of cancer to a fatal outcome. For example, a cell can mutate into cancer but if a tumor can’t grow the new blood vessels it needs to supply itself with nutrients, the cancerous cell can’t make a mass. This link in the cancer chain is targeted by anti-angiogenesis drugs. Likewise, cancer cells depend on rushing through the cell cycle, crashing through gates that limit the growth of healthy cells—chemotherapy sits at these checkpoints killing the fast-dividing gate crashers. Basically, by looking at the lifecycle of cancer cells or at the progression of the entire tumor ecosystem, researchers can discover these bottlenecks through which cancer must travel in order to be deadly. Plug one of these bottlenecks and cancer can’t reach its endpoint. As you might guess, one of the most important hoops cancer jumps through on this path is metastasis. That’s because many cancers don’t kill at their sites of origin. For example, nobody dies of localized prostate cancer. It’s only when the cancer metastasizes to bones, lymph nodes, lungs, liver or brain that the disease turns deadly. Likewise, bladder cancer doesn’t kill in the bladder and if it would stay put, the disease would be largely manageable. Staying put is the default of healthy epithelial cells—the ones that when mutated generally give rise to bladder cancer. These healthy cells must attach and stay attached to their surroundings—cells that accidentally break free know they’ve come unmoored and generally die of the programmed cell death known as annoikis. Bladder cancer that metastasizes has learned to evade this control. ANDROGEN RECEPTORS IN BLADDER CANCER CU Cancer Center researchers in the Theodorescu Lab have been at the forefront of work showing that a major mechanism that bladder and many other cancers use to attach at new sites of metastasis is over-expressing a protein called CD24. Think of it like growth-promoting glue. A bladder cancer cell mutates in a way that ramps up production of CD24. Then when it floats through the bloodstream, it uses this protein to glue itself to new sites and to stimulate its growth at the metastatic site such as the liver or bones. Sure enough, Theodorescu has shown that bladder tumors with higher levels of CD24 have poorer prognoses. What leads to the over-production of CD24? If you guessed androgen, you’re right. In a major paper published in the Proceedings of the National Academy of Sciences, Theodorescu showed that mice whose tumors had higher CD24 did worse—especially the male mice. Likewise, it was male bladder cancer tumors that carried poor prognosis along with high CD24. “More than three times as many men than women are diagnosed with bladder cancer,” Theodorescu says. “To us, these sex-specific findings implied androgen involvement.” Like Richer and Elias’ work with androgen in breast cancer, the story of androgen in bladder cancer has gone from clinical observation to the lab and should soon make its way back to the clinic. Theodorescu showed that androgen directly regulates CD24, which in turn, is an important driver of bladder cancer metastasis. Now, “to me, it’s not a question of whether we should be testing anti-androgen drugs in bladder cancer patients, but in what settings,” Theodorescu says. “For example, when you look for androgen receptors in bladder cancer, a third of the cancers light up, a third if you squint the right way you can convince yourself they light up, and a third don’t express the androgen receptors at all.” “Fundamentally the question I’m struggling with is how much androgen does a bladder cancer need in order to grow and hurt the patient?” Theodorescu says. “How many receptors make drugging with anti-androgens worthwhile?” With prostate cancer, anti-androgen therapy is part of the standard of care. With breast cancer, it’s pushing toward the standard. And in bladder cancer, anti-androgen therapy is just now exploring its first foray away from the lab and into patients. Soon, though, with a target in sight and good drugs already in hand, the same knob that Arnold turned up to signal the growth of his muscles, doctors may be able to turn down or stop the growth of many cancers. 8 WWW.COLORADOCANCERCENTER.ORG DEC DING CANCER HOW DOCTORS BREAK CANCER’S CELL SIGNALING E very cell in your body holds the DNA needed to manufacture the tissues and chemical signals your body needs throughout your life—from the signals of rapid cell growth that HERE’S HOW IT WORKS: Cells have “receptors.” These receptors generally live in two places: 1. receptors on the surface of the cell membrane grab things floating around in the blood—thus activated, they relay signals inside the cell; 2. receptors floating in the cell’s cytoplasm look for things like hormones that naturally diffuse through cell membranes; when these intracellular receptors grab something like estrogen or androgen, they are activated and send the signal inside the cell’s nucleus where the signal can interact with and influence the cell’s DNA. Receptors are fairly specialized to grab only certain things. An estrogen receptor grabs estrogen. An androgen receptor grabs androgen. By breaking this signaling chain, modern medicines are learning to break cancer. turn a fertilized egg into a baby, to the ability to create specialized tissues like brain and liver and fingernail cells. But a brain cell doesn’t need to make skin tissue and adult cells don’t need to divide like embryonic cells, and so your body’s cells have developed a complex network of on/off switches that lets them make stuff only when and where you need it. Your body flips these switches to regulate things like tissue repair, immunity and homeostasis. Cancer has also learned to flip these switches. Accidental mutations can turn on signaling that should be silent, leading cells to manufacture inappropriate things and behave in inappropriate ways. For example, some cancer cells have learned to restart the signaling that leads to embryonic-like growth, which in the adult body lets cancer cells replicate far faster than surrounding, healthy tissues. COMMON PLACES DOCTORS BREAK THE CHAIN OF CANCER’S GROWTH SIGNALING: HOW CANCER GROWS: Hormones or other signaling molecules are produced and circulate through the bloodstream Receptors specialized to “grab” these signaling molecules coat cell surfaces or float inside cells’ cytoplasm Receptors grab signaling molecules Receptors are activated and relay a message deeper into the cell HOW DOCTORS STOP CANCER: Drugs like leuprolide stop the signals that tell testes to produce testosterone that can drive prostate cancer, and aromatase inhibitors stop the production of estrogen that can drive breast cancer—no signaling molecule equals no signal Drugs like faslodex make breast cancer cells express fewer estrogen receptors (and make existing ones work less well) Drugs like tamoxifen plug estrogen receptors without activating their signal. With tamoxifen in place, estrogen receptors can’t grab estrogen The drug enzalutamide (profiled in this article) makes cancer cells unable to transmit signals inside their nuclei, where the signal could affect cells’ genetic behavior 9 C3: SPRING 2013 A CONVERSATION WITH RAJESH AGARWAL, PHD Co-program leader of Cancer Prevention and Control at CU Cancer Center Professor at the Skaggs School of Pharmacy and Pharmaceutical Sciences BY GA RT H S U N D E M After earning a PhD in organic chemistry, a post-doc position in a cancer lab helped Rajesh Agarwal make the transition to cancer science. Now 30 years later, Agarwal is one of the most accomplished scientists looking to naturally occurring compounds for the prevention and control of cancer. Here we talk with Dr. Agarwal about his work. C3: In last few years, you’ve published exciting findings with compounds derived from milk thistle, grape seed and bitter melon, to name a few. This work has been featured in top journals including JNCI, Cancer Research, etc. Do you think it’s been difficult to find acceptance for your work within the scientific community specifically because you work with “natural” compounds? Agarwal: Actually, you wouldn’t know it but many of the cancer medicines now in use were derived from sources in nature. Just because a compound comes from a flower or a fruit or a melon, doesn’t mean that it is any more or less potent than compounds that were engineered from scratch in a laboratory. C3: So is it safe to say that eating or otherwise using these natural compounds people and help the prognosis for people diagnosed with cancer? Agarwal: Let me tell you a story. After we published the most recent article on bitter melon [which was found to selectively kill pancreatic cancer cells], I had literally hundreds of phone calls, hundreds of e-mails. But I didn’t have one call from a person unaffected by cancer. Everyone—he or she or a loved one—was having a pancreatic cancer issue. can help reduce the cancer risk for healthy C3: You’ve been at this 30 years now. In that time, have you seen the culture of studying “natural” compounds change? Agarwal: Certainly. It used to be that we would simply test compounds for activity—we would treat cancer cells with silibinin [from milk thistle] or grape seed extract and notice how the cancer cells or animal models were affected. Recently, we’ve seen a major shift toward asking not only if compounds People who are suffering have more connection with this kind of research. So it’s much easier to study the effectiveness of these compounds in treating cancer than it is to study their use in prevention. So yes, we know that these compounds are active in treating cancer. We have population evidence to show they’re active in preventing cancer, but proving their effectiveness in prevention is much more difficult. are effective but why they are effective. The thing is, cell biology and molecular biology keep advancing and now we have the tools to ask questions we couldn’t ask before. We’re looking at how these compounds work—what genes and pathways within the cell they target—so that we can refine these treatments. C3: How is the funding climate for research with natural compounds? Agarwal: So, you know, I just came back from the meeting of the American Association for Cancer Research. Everyone there was worried about funding. It’s a hard climate and the number of grants being funded is dropping really fast. It’s not a matter of your compound—it’s hard for everyone. I think it’s especially hard for young scientists, but I started my grant 20 years ago and my lab continues to work with three active R01 grants. I’ve learned to keep working on what you want to study—to go where your interest and expertise lead. As a scientist, my job is to find anything that could eventually be effective in people. That’s my goal anyway. Learn more about Dr. Agarwal’s research by searching “Agarwal” on www.coloradocancerblogs.org Rajesh Agarwal, PhD, shows that natural compounds derived from milk thistle, grape seed and bitter melon may combat or even prevent a range of cancers. 10 WWW.COLORADOCANCERCENTER.ORG CASEY CAS S Finding a way back to “normal” JANA LO MA X H E LP S CAN C E R PAT I E NTS ADJ UST TO L I F E AFTE R D I AG N O S I S BY E R I K A MATI C H As a child, Jana Lomax, PsyD, sat at the dinner table listening to her parents’ conversations about the psychological needs of the patients they saw that day. Her father, an urologist, and mother, a nurse, often worried their patients wouldn’t get the support they desperately needed after learning about their cancer diagnosis or other life-threatening disease. Once she became an adult, Lomax took those conversations to heart. She found a way to help cancer patients navigate cancer’s emotional journey, along with the physical one, and became a clinical health psychologist. “My father would ask how to support those patients and where to send them. The options were limited in rural Indiana,” Lomax says. “I was lucky enough to find a career to meet that need.” Lomax went to Miami University in Oxford, Ohio, with the goal of finding a career to help people deal with the challenges that accompany cancer and chronic conditions. She earned a psychology degree and later completed a doctorate in clinical psychology at Illinois School of Professional Psychology at Argosy University in Chicago. In 2004, Lomax moved to Colorado and found a position with University of Colorado Cancer Center’s Cancer Information and Counseling Line (CICL), a nationally recognized service offering free phone support for people with cancer and their families and friends. Lomax was finally meeting her goal of working in the oncology community. Eventually, she was offered a job in the Hematology Malignancies and Blood & Marrow Transplant Program. Today, Lomax is a cancer prevention and control researcher at CU Cancer Center and director of psychosocial oncology at Exempla Saint Joseph Hospital and Exempla Good Samaritan Medical Center. Leading a team of social workers, dietitians and residents, Lomax works with oncologists and allied health professionals to help cancer survivors manage the adjustments that come with their diagnoses. Regardless of age or stage of cancer, patients come to Lomax and her team to discuss ways to cope with the fears, anxieties and stress a new cancer diagnosis can bring. Post-treatment, Lomax also helps patients find their way back to “normal” life or the “new normal.” “Cancer can often motivate people to make meaningful life changes. They want to live a fulfilling life after facing mortality. I get to help them find meaning, have difficult conversations and resolve difficult relationships,” Lomax says. “I help people answer questions like: how do I make sure my 3-year-old remembers me as a good mother who lived fully?” Lomax spends much of her time developing survivorship programs like CU Cancer Center’s LIVESTRONG Cancer Survivorship Program, which offers clinical services for cancer survivors and assesses their ongoing needs. “It’s satisfying to take what we know works for cancer survivors to a wider audience, especially to people who may not know how many resources are available now,” says Lomax, who is also working on a pilot program that makes information about cancer available online to those who are newly diagnosed. Stress is one aspect of dealing with cancer that Lomax knows well, both from her patients’ perspectives and her own. “The research we have is inconclusive in terms of mood and how that links to cancer progression. But there is evidence that chronic stress can affect our immune system. I help people do the work that may help them heal and manage their stress and hopefully reduce risks of recurrence, but at minimum improve their quality of life,” Lomax says. “I want to hear that they are angry; I want them to feel open to having bad days. “But I want them to manage their stress differently and understand where that comes from and develop healthy, adaptive ways of coping. Whether that is deep breathing or throwing a pillow across the room or listening to music,” she says. Because her job can also bring stress to her own life, Lomax dedicates uninterrupted time to her family and doesn’t make promises she can’t keep, a perspective she learned long ago at the kitchen table. “I learned that perspective from my dad,” Lomax says. “Helping people is so rewarding so I focus on helping people live better and make the most of what they have.” JANA BOLDUAN LOMAX, PsyD Clinical Health Psychologist University of Colorado Cancer Center Director of Psychosocial Oncology Exempla Saint Joseph Hospital and Exempla Good Samaritan Medical Center SU RVIVO R S H I P RESOURCES Cancer Information & Counseling Line (800) 525-3777 The Monfort Family Foundation Cancer Resource Center University of Colorado Hospital (720) 848-0316 LIVESTRONG Cancer Survivorship Programs • University of Colorado Hospital, Aurora (720) 848-0349 • St. Mary’s Regional Cancer Center, Grand Junction (970) 298-7500 • St.Mary-Corwin Medical Center, Pueblo. (719) 557-3738 Psychosocial Oncology Support Services Exempla Saint Joseph Hospital Comprehensive Cancer Center, Denver (303) 318-1322 11 C3: SPRING 2013 KIM C H RISC ADE N MD CLINICAL CARE BY K I M C H R I SCA D E N reserving P OPTIONS YOUNG CANCER PATIENT FORCED TO MAKE FERTILITY A PRESENT ISSUE doctor didn’t know if it could be cancer. Further examinations were needed. A mammogram couldn’t detect the lump so she was sent for an ultrasound and biopsy. Then the waiting began. A little over a week after Bri’s self-examination, the phone rang. “My doctor called me back on a Saturday, so I instantly knew the news wasn’t positive,” Bri says. With her sister by her side, Bri listened to the news: stage I breast cancer. At less than a centimeter, the tumor had yet to spread. Bri’s self-examination had caught the cancer early. “I always assumed if I found out I had cancer I’d immediately start crying, but I was just in shock,” Bri says. “As I listened to my doctor, I couldn’t stop shaking or process what she was saying.” At 24, Bri Pasko hadn’t thought much about children, besides assuming she’d have them one day. Then on Feb. 10, 2012, Bri jumped in the shower to begin her usual morning routine and for some reason, gave herself a breast self-examination. “I hadn’t been good about regularly preforming self-breast exams and assumed the exams my doctor performed at my physical once a year would suffice,” says Bri. “I figured since breast cancer ran in my family, I needed to start doing them.” In her left breast, Bri felt what no woman ever wants to feel—a hard, pea-sized lump. “I didn’t know if this was normal or not, so I instantly called my primary care provider.” Twenty-four hours later she found herself at the doctor’s office. Because of Bri’s age and the size of the lump, her 12 WWW.COLORADOCANCERCENTER.ORG PAT RIC K C AMPBE LL S E E K I N G S P E C I AL I Z E D CAR E Every year, 27,000 women under the age of 45 are diagnosed with breast cancer. Compared to the more than 200,000 cases in women over 45, Bri’s cancer was considered uncommon. It was also considered treatable. She’d need to have a lumpectomy and undergo six weeks of radiation. Prior to treatment, Bri and her boyfriend, Scott Bradley, decided to get a second opinion. After searching the internet for the best breast cancer specialists, Scott learned the University of Colorado Cancer Center had a young women’s breast cancer program. They were advised to schedule an appointment with Virginia Borges, MD, MMSC, director of the Young Women’s Breast Cancer Translational Program. “I wanted Bri to go to the best of the best,” says Scott, admitting he researched multiple places out-of-state. “We ended up coming to the University of Colorado because of the multidisciplinary clinic and the ability to have our case reviewed by multiple physicians.” It turns out Bri was also looking for a particular oncologist— one who didn’t see her as the average breast cancer patient. “I ended up choosing Dr. Borges as my physician because I didn’t want to be treated as a 60-year-old breast cancer patient. I wanted someone who understood where I was in life and could address the concerns of someone in their 20’s,” Bri says. Borges’ clinic was exactly where Bri needed to be, as patients under the age of 45 are her only clientele. The specialized clinic is tailored to the needs of younger patients whose reactions to drugs, life issues and presentations of breast cancer are different than older women, explains Borges. “A 24-year-old woman can walk into my clinic and she’s not rare,” Borges says. “She’s one of many her age who are also sitting in the waiting room with the same concerns.” Fertility is one of the first topics Borges discusses with her patients during their initial assessment. Because cancer treatments can increase or decrease fertility, Borges assesses each patient to learn where she stands when it comes to reproduction. Does the patient want a family? Is the patient done having children? Does the patient already have children but want more? Bri was asked these questions from day one. Though she wanted children, she never thought fertility would be an issue. Borges referred her to Laxmi Kondapalli, MD, MSCE, head of CU Cancer Center’s new Oncofertility Program for fertility counseling. Prior to Kondapalli’s program, Borges would have sent patients to multiple specialists depending on their reproductive needs. Now, the program provides a one-stop shop for all cancer patients, male and female, to understand their fertility in the face of a cancer diagnosis. “Now that we have the Oncofertility Program, I always tell my patients on the first day I meet them, ‘go see Dr. Kondapalli. She’ll take care of everything and answer all of your questions,’” Borges says. WAITI N G F IVE YEAR S Often oncologists face a tough balancing act between aggressively treating their young patients’ cancer as soon as possible and taking the time to preserve their fertility. At CU Cancer Center, oncologists are working to refer their patients to the Oncofertility Program prior to treatment—as many lifesaving cancer treatments can severely limit the chances of having a biological family in the future. In women, chemotherapy can damage eggs stored in the ovaries and radiation can damage the uterus. For men, treatments can affect both sperm quality and sexual function. Laxmi Kondapalli, MD, MSCE, Unfortunately, a lot of patients aren’t aware of head of CU Cancer Center’s new Oncofertility Program the risk factors. “When making treatment decisions, a lot of cancer patients aren’t informed about how each one will affect their fertility in the future,” Kondapalli says. “When patients come to my clinic, I want to make sure all of their reproductive health and fertility questions are answered so that when they leave, they have a clear idea of how their treatments may impact their fertility in the future.” C ASE Y C ASS “I NEVER THOUGHT I’D HAVE TO WORRY ABOUT FERTILITY CONCERNS, BUT ESPECIALLY NOT AT 24 YEARS OLD.” In 2012, the Oncofertility Program’s first year, Kondapalli saw 160 patients, of which 40 percent where male. Bri was one of those 160. Though her cancer treatment was relatively simple, she needed to understand its impact on her fertility. Bri met with Kondapalli for a full fertility overview and blood analysis to evaluate her current reproductive state. This included ovarian reserve testing to gain a count of Bri’s eggs. All of the results were good. Bri’s egg supply was high. Her treatments weren’t going to impact fertility in the long-term. “I was so lucky to not have to go through chemo,” says Bri. “We were just so thrilled. Up until this process, I never thought I’d have to worry about fertility concerns, but especially not at 24 years old.” Still, Bri has at least five years of cancer treatment in front of her, as she is currently taking tamoxifen, an estrogen blocker used to prevent recurrence. The drug is not safe during pregnancy, so Bri is advised to wait the full five years before starting her family. Young women can interrupt their years on tamoxifen in order to have children, but those decisions are made very individually for each woman. “We decided to wait the full five years before having kids because of Bri’s age and because she had an estrogen-receptor tumor. Hopefully, I won’t be in a wheelchair by the time we have kids,” jokes Scott, who is 30. 13 C3: SPRING 2013 Finding ways to keep their minds off Bri’s diagnosis, Scott and Bri began experimenting in the kitchen. Twenty-four recipes turned into Smart Cookie Treats—an allnatural, made-to-order dog treat company. K E E P I N G TH I N G S N O R MAL Though Scott and Bri had been dating since 2009, they hadn’t thought much about what life would be like in five, 10 years. They didn’t expect breast cancer to propel them into the future. Besides fertility and treatment being top-of-mind, Bri needed to know if Scott was in for the long-haul. “I told Scott from the beginning, if you want to get out, now is the time to do so,” she says. “If not, you’re sticking with me through this.” Scott not only stuck with Bri, he launched into full support mode. The day after diagnosis, the couple decided to build a “kitty condo” for Bri’s new savannah cat, Bentley. Though Scott wasn’t a fan of cats, Bentley was a great way for Bri to keep her mind off the diagnosis. “I remember finding her in the garage and just knowing we were going to get through this,” Scott says. “She showed me from the beginning her strength, not to mention, she was using power tools to build this kitty condo which was pretty hot.” Working full-time and going to multiple doctors’ appointments wasn’t enough to keep Bri and Scott’s mind off the cancer. They still had the evenings. To fill the time, they went into health lockdown making sure they only put the freshest ingredients into their bodies. Sam, their golden retriever, and Bentley were included. Within weeks, the couple was in their kitchen most nights until 2 a.m. They weren’t making food for themselves; rather they were coming up with the perfect all-natural dog treat recipes. Twenty-four recipes turned into Smart Cookie Treats— an all-natural, made-to-order dog treat company. “I knew I needed to find a way to keep things normal for the both of us,” says Scott. “Starting a business was my weird way of doing it.” Smart Cookie Treats has done better than the couple expected. The treats are mainly sold online and in a few local stores, but they hope to expand to selling treats at local parks. Life is back to “normal” for the two of them. PAT RIC K C AMPBE LL P UTTI N G CAN C E R TO TH E S I D E Today, the couple doesn’t think much about Bri’s cancer besides her daily reminder—tamoxifen. “I’d be lying if I didn’t think about my breast cancer every day,” says Bri, “but now it’s more at the back of my mind.” Instead, the couple is planning for their next big step—marriage. On Nov. 7, 2012, Scott proposed to Bri in at the Angkor Wat Temple in Cambodia. Though he had a 17-hour flight to come up with the perfect proposal, the first words that came out of his mouth were, “you’re the bacon to my eggs,” he recalls, laughing. Bri didn’t expect the proposal nor suspect anything by Scott’s weird behavior. “He was acting so strange moving us from one spot to another and saying ‘it’s a better view over here or let’s take pictures over there,’” she remembers. “I didn’t even realize he was going to propose.” While not the “perfect” proposal, the couple still laughs about the moment to this day. Bri and Scott hope to get married in Mexico in fall 2014. “I see us as very fortunate. Most people are taking a leap of faith when they get married,” says Scott. “They haven’t had to go through the hard stuff or see their significant other’s true colors during a hard time. We’ve made it through all of that.” While the couple may wait five years to start a family, they’re finding plenty of ways to stay busy. With a dog, cat and growing business, they’re never short of things to do. Luckily, breast cancer isn’t one of them—Bri is cancer free. PATRICK CAM PBELL Visit Smart Cookie Treats at www.smartcookietreats.com. Bri and Scott with Sam, their inspiration for the new business. 14 WWW.COLORADOCANCERCENTER.ORG ST RY INSIDE Oncofertility program gives hope to young cancer patients desiring families Through oncofertility specialists, patients like Bri Pasko (page 12) are now being counseled about options available to help maintain fertility prior to cancer treatment. Today, oncologists at the University of Colorado Cancer Center are referring patients of childbearing age to its new Oncofertility Program. F or some young people, cancer treatments such as chemotherapy and radiation used to save their lives can also limit their ability to have biological children in the future. With the increase in cancer survivors, physicians are beginning to focus not only on treatment but also quality of life post-treatment. In 2012, the University of Colorado Cancer Center launched its Oncofertility Program—one of only a handful in the country that provide a multidisciplinary approach to cancer treatment planning and care. Headed by Laxmi Kondapalli, MD, MSCE, assistant professor of reproductive endocrinology and infertility at CU School of Medicine, the program provides clear family planning options for male and female patients, community support services, research, and education to doctors and hospital social workers. According to a recent survey, less than half of all oncologists routinely refer patients to a fertility specialist prior to initiating cancer treatment. Kondapalli is working to increase those numbers and help patients address one of their biggest concerns: infertility. At CU Cancer Center, Kondapalli is developing best practices for referring patients to the Oncofertility Program. One of those best practices is creating a simple check box within the electronic medical records for physicians to check if their female patients are under the age of 45 or if their male patients are under the age of 60. By singling out specific age groups, Kondapalli will be able to recognize which patients may need fertility preservation and oncofertility services. “We hope this is a way for patients to get streamlined to our clinic, while gently reminding providers to think about each patient’s fertility issues,” Kondapalli says. Last year, the program saw 160 adult and pediatric patients, of which 40 percent were male—a success due in part to referring oncologists at the Cancer Center. “What’s helped our program grow is that our oncologists at the Cancer Center are really collaborative,” Kondapalli says. “They think about survivorship care from the beginning of treatment and know where to point their patients who may have fertility questions.” Kondapalli has also streamlined the process of getting patients in the door. In addition to Kondapalli, a physician assistant, a scheduler, and a nurse manage the entire caseload, and make sure each patient is seen within 48 hours of referral. “Our patients see us as a team,” says Kondapalli. “They don’t have to be shuffled from one person to the next. We know each one of them and their individual needs.” Another unique component of the program is the fluidity between oncofertility clinical care and research, as all of Kondapalli’s patients have the option to join her oncofertility registry for future research projects. Currently, Kondapalli uses the registry to study how treatments can impact ovarian reserve and how hormonal function in cancer survivors can put them at greater risk for other chronic diseases. While Kondapalli says very little research has looked into how today’s cancer treatments impact fertility in the long term, she believes prevention is key. “Since our patients aren’t infertile, but instead at risk for being infertile in the future, we see oncofertility as a prevention measure,” she says. And “as technologies continue to improve, I think that oncologists and other physicians will continue to see oncofertility as hope for their patients now and well into the future.” —Kim Chriscaden The Oncofertility Program sees cancer patients and their significant others for the following concerns: • Cancer Risk Reduction • Contraception • Fertility Preservation — Egg, embryo, sperm and ovarian tissue freezing — Ovarian transposition • Hormone Replacement Therapy • In Vitro Fertilization • Oncofertility Consultation • Ovarian Reserve Testing • Preconception Counseling • Sexual Functioning • Third-party Reproduction For a complete list of services, please visit: http://arm.coloradowomenshealth.com or call 303-724-FERT (3378) to schedule an appointment. 15 C3: SPRING 2013 CONNECTING THE DOTS B Y M A RY W. L E M M A For Patients, Knowledge is Power at Hereditary Cancer Clinic aria Ostling, 50, is a self-described “information junkie.” She’s online, ferreting out all she can and connecting with people who have the same hereditary condition that she and several family members have: Lynch syndrome. Maria refers to these online support networks as “Lynchville.” Lynch syndrome is caused by inheritance of a genetic mutation that significantly increases the risks of several kinds of cancers, particularly colorectal cancer and, in women, uterine and ovarian cancers, says Dennis Ahnen, MD, a gastroenterologist at Denver VA Medical Center and consultant at the University of Colorado Cancer Center’s Hereditary Cancer Clinic. Maria’s father developed cancer of the bladder at 26, colo rectal cancer at 45 and died of cancer of the duodenum at 61. Maria’s sister Kitty, now 40, was diagnosed with colon cancer at 26. Their mother has lymphoma. An aunt died of breast cancer. But until fairly recently, none of the siblings’ health care providers connected the dots. “For 12 years I’ve gone to doctors and written down my family history,” says Maria, who has two daughters and five grandchildren. “So have my brother and sister. And for 12 years, no one turned in his chair and looked at me and asked, ‘Has your family been studied?’ ” It was the oncologist treating Maria’s mother who finally connected the dots, raising the possibility of Lynch syndrome. Early in 2012, Maria accompanied her sister to a meeting with Michelle Springer, one of three genetic counselors at the Hereditary Cancer Clinic. Genetic counselors are the liaisons between the patient and physician, says Springer, who has been counseling patients for 14 years. Before she meets with patients, Springer collects information about the history of cancer in their family—as she did with Maria and her siblings—by way of a six-page questionnaire that asks about parents, siblings, grandparents, nieces and other family members. Using software, Springer creates a threegeneration family pedigree, which she then uses to create a risk Maria Ostling and her daughter, Brittany Justice both tested positive for Lynch syndrome, which increases their risk for several types of cancer. calculation. Then she meets with the family—in this case, Kitty and Maria—for a thorough review of the findings. “We’re trying to figure out the underlying cause of a cancer and whether there could be an inherited component to it,” Springer says. “While the vast majority (80-90 percent) of all cancers are sporadic, we know that about 10 percent of cases are hereditary, meaning that the person inherited an abnormal copy of a gene that puts them at higher risk.” Lynch Syndrome accounts for about 3-5 percent of colon cancers. “Our clinic sees all types of patients with a personal and/or family history of cancer, including many families concerned about their risk of breast and colon cancer. One of the things we know about Lynch syndrome is that it’s highly under-diagnosed,” Springer says, “which is why many families go undetected.” There is a huge push to increase education, awareness and testing for Lynch syndrome. The more the clinic can identify 16 WWW.COLORADOCANCERCENTER.ORG COURTESY OF MARIA OSTLING M Dennis Ahnen, MD, a gastroenterologist at Denver VA Medical Center and consultant at CU Cancer Center’s Hereditary Cancer Clinic, explains a colonoscopy procedure. families at higher risk of developing cancer, the better the families will be at identifying their cancers earlier, if they do develop. The Hereditary Cancer Clinic is unique in its design, Ahnen says. “Ours is different from most similar clinics in that everyone who comes for an appointment is seen by a clinician as well as a genetic counselor.” In addition to Ahnen, Catherine Klein, MD, oversees weekly clinics with the genetic counselors, including Springer, Lisen Axell and Lisa Ku. As thorough as genetic counselors like Michelle Springer are, it’s critical that a physician specializing in that patient’s cancer risk is present. “Dr. Ahnen created a life plan—a roadmap for what we need to do,” Maria says. “They were very patient oriented. I’ve talked to a lot of people who have Lynch but don’t have that roadmap. It’s sad out there.” Maria’s 27-year-old daughter tested positive for Lynch, as did Maria’s brother Curt, who says he was “shocked” because his health history and screenings have been clear. He admits to being less active than his sister in communicating about the syndrome, but he’s completely on board for his son to be tested (fortunately, so is his son). The lifetime risk for colon cancer is about 50 percent in families with Lynch syndrome. “When we get family histories, we identify the cancer with molecular information from the tumor tissue; then we can suggest gene testing,” Ahnen says. “If the family agrees to the testing, we arrange genetic testing and if a diseasecausing mutation is found we help design a plan for cancer screening and prevention. For mutation carriers, we typically recommend a colonoscopy at 25 and every one to two years thereafter.” For women with a higher risk of endometrial and uterine cancers, clinicians recommend endometrial aspirates and pelvic exams at 25 years of age. After children, Ahnen says, patients should consider a prophylactic hysterectomy and oophorectomy (removal of the ovaries) to prevent cancers of these organs. Maria and Kitty have both had the prophylactic surgery. The biggest call to action for individuals: Know your family history. “Ask questions of your family members. Most people know what medical conditions their parents and siblings have had or how they died,” Ahnen says, “but many don’t have information beyond that. Talk to your provider about your history. Knowledge of your cancer family history doesn’t do as much good if your provider doesn’t know about it. Knowing this information is critical because it changes our medical management and screening recommendations.” As one of Springer’s patients agrees, “Knowledge is power.” “If your provider has any uncertainty, talk to a genetic counselor about whether you’d benefit from genetic testing,” Ahnen says. “Counselors here have done a great job of collaborating to make genetic testing available.” Springer reassures patients that not everyone who has tested positive for Lynch will develop cancer. “I always tell patients that having Lynch syndrome is not a death sentence, as many of the cancers associated with Lynch syndrome can be prevented.” Still, screening—even when it’s limited for some kinds of cancer—is crucial for everyone. Maria Ostling had a colonoscopy in 2012, and they removed a pre-cancerous polyp. The previous diagnosis of Lynch syndrome prompted her to have another colonoscopy just one year later (it was clear). “Had I waited, I would have had full-blown colon cancer by now because polyps can progress so much more rapidly in families with Lynch,” Maria says. “And had my sister not gone through what she had, and been tested, I wouldn’t have known about this. “Someone’s watching over us. My family may have Lynch, but Lynch won’t have my family.” C ASE Y C ASS 17 C3: SPRING 2013 S U P P O R T E R F CUS MARY W. LE MMA A Legacy of Giving (and Golf ) CAR MOS I NO FOR M S TH E ROCKY MOU NTAI N ITALIAN GOLF ASSOCIATION WITH A S PECI FIC GOAL I N M I N D B Y M A RY W. L E M M A On Al Carmosino’s trips to Italy, he tours prosciutto, cheese and balsamic vinegar factories rather than churches. To him, that same aesthetic is an important part of his yearly golf tournament that raises money for CU Cancer Center. “Churches are beautiful, but after a while they all look the same,” says Carmosino, 82 and a semiretired attorney from Evergreen. Likewise, “you go to some golf tournaments and get a hot dog, but we wanted to keep the Italian culture going. We put on a full sit-down dinner with sausage, peppers, pasta and an open bar.” Not to mention donated entertainment like Perry Como, whose personal music arranger was a Denverite and friend of the group. Carmosino lost his mother to uterine cancer and his father to stomach cancer. In the 1980s he joined a golf group based in Palm Springs, Calif. that was raising money for charity and thought he’d try something similar a little closer to home. “My friend just said, ‘Get it done, kid’,” Carmosino recalls, “so we tried it here and it worked.” In 1989 the Rocky Mountain Italian Golf Association was born for one simple purpose: “Cure cancer,” Carmosino says. Carmosino wouldn’t have it any other way. “It was a party, a festival,” Carmosino says. Nearly 80 golfers have participated in each tournament through the years. “Perry Como brought a lot of people with him, so it mushroomed.” At $650 a head, including the big-name entertainment, which was donated, and three days of golf and bocce, it was a successful benefit for the Cancer Center, raising more than half a million dollars over more than two decades. The group provided the food for the hotel to prepare and serve; various refreshments, wine and the bar were donated. COURTESY OF AL CARMOS INO Since then, Carmosino, his wife Mildred and their many friends have organized yearly golf tournaments at the Inverness Hotel lasting three days and featuring out-of-town talents including—in addition to Como—singer Buddy Greco, Danny and the Juniors and The Four Aces. And of course, plenty of good Italian food and drink. “I’m just one of many people who give their time to this kind of thing.” For more than two decades, Al Carmosino has been bringing Italy to his Rocky Mountain Italian Golf Association. “People have been coming for years,” Carmosino says, “but a lot of the ones who started the tournament aren’t here anymore.” The economy also had an impact on the three-day benefit, so early in the last decade, the tournament was scaled back to one day. “People have been bugging me to organize another one, so we’ll probably have one tournament next September.” The events take about six months to organize and everyone involved is a volunteer. Carmosino adds that no one, not even the personnel who work the golf course, is paid. In its early days, you had to be Italian to be part of the Rocky Mountain Italian Golf Association, but that ended long ago. In fact, the association has no membership per sé; it’s just a 501(c)3 entity that supports charity. Playing in the tournament is by invitation. “If you get out of line, like drink too much, you aren’t invited back,” Carmosino says. Carmosino graduated from the University of Denver law school in 1955 and has been in practice since then. “It was great in those days,” he says, “because no one really specialized, so you got to know the profession really well.” Today, in his office in Northglenn, Carmosino is semi-retired and works mostly with wills and trusts. But Carmosino is still focused on charity—and having fun while supporting it. “My main goal is to help find a cure for cancer,” he says. “I’m just one of many people who give their Joe Terry, Al Carmosino, Perry Como, Frank Mattei and Ed Weiman at the 1989 golf tournament. time to this kind of thing.” 18 WWW.COLORADOCANCERCENTER.ORG C O M M U N I T Y N E W S S AV E T H E D A T E AUGUST 3 — DINNER IN WHITE Join the University of Colorado Cancer Center Fund at the summer’s most popular fundraising event—the 4th annual Dinner in White. Dress in white, pack a picnic dinner and enjoy an evening dancing under the stars. Text messages and posts on social media will reveal this year’s secret location an hour before the event. Tickets can be purchased for $50 at www.dinnerinwhite.com. STEVE Z PHOTOGRAPHY On August 15, 2013 the Eldorado Springs Cure will celebrate its 35th Anniversary. ELDORADO SPRINGS CURE RUN CELEBRATES 35 YEARS Thirty-five years ago Stan Havlick’s first wife was diagnosed with acute lymphocytic leukemia. Shortly after, he used his strong business skills and passion for the outdoors to create the Eldorado Springs Cure—a four-mile benefit run held every summer in Eldorado Springs, Colo. “I felt quite helpless at the time,” recalls Havlick. “With three children and a house under construction, I went to the doctors and asked how I could help. They needed new lab equipment and faculty start up funds so I figured I could use my business skills to help raise some money.” Three decades later, the small summer race turned into the main fundraising event for the Colorado Cancer Foundation which provides meaningful resources for the University of Colorado Cancer Center and local cancer patients needing financial assistance. “The Colorado Cancer Foundation is a grassroots, hands-on organization that generates small donations for cancer research, laboratory equipment and patient assistance in Colorado,” Havlick says. The Eldorado Springs Cure was first held in Eldorado Springs because William Robinson, MD, PhD, a CU Cancer Center physician who treated Havlick’s wife, was living there at the time. Though Robinson no longer lives in Eldorado Springs, the race still starts and finishes at the Eldorado Springs Resort and Pool. “Not only is The Eldorado Spring Cure considered the oldest benefit race in Colorado, it’s probably one of the most scenic,” Havlick says. “Besides running near the picturesque canyon, runners and their families get to enjoy the Eldorado Springs Pool and delicious cuisine when they are finished.” The Eldorado Springs Cure will take place on Thursday, August 15 at 6:30 p.m. and is open to all runners—kids, dogs and elite racers included. Register for the event at www.myentryfee.com. Preregistration is $25 and race day registration is $30. Learn more about the Colorado Cancer Foundation at http://co-cancer-foundation.org. NEW PARTNERSHIP RAISES AWARENESS OF PANCREATIC CANCER University of Colorado Cancer Center and Wings of Hope for Pancreatic Cancer Research have joined forces to raise aware- UPCOMING EVENTS • June 22-23: Front Range Cancer Challenge • June 23: Naren A. Vora Golf Tournament • July 12: Over the Edge rappelling fundraiser • July 28-29: Golfers Against Cancer Gala and Tournament • August 18: Race for Research 5k For more details about these events, visit COCKTAILS FOR A CURE RAISES $146K FOR WOMEN’S CANCER RESEARCH CU Cancer Center Fund’s annual women’s event, Cocktails for a Cure, raised $146,000 for women’s cancer research. Nearly 350 women enjoyed signature cocktails from local bartenders, bid in a silent auction and listened to a survivor’s story. Proceeds from this year’s event benefited the research of Drs. Heide Ford, Laxmi Kondapalli and Jennifer Richer. ness about pancreatic cancer and boost funding for pancreatic cancer research. Pancreatic cancer is the 4th leading cause of cancer death in the United States and is projected to rise to the 2nd leading cause by 2020. It is estimated that 43,000 Americans are diagnosed each year with pancreatic cancer; 74 percent will not survive longer than 12 months. “There is no broadly accepted early detection method for pancreatic cancer and effective treatments are limited,” says Colin Weekes, MD, PhD, CU Cancer Center medical oncologist. “We hope to improve the outlook for people with pancreatic cancer by discovering and developing biologically targeted therapies.” Wings of Hope was founded in February of 2012 by Maureen Shul, the former mayor of Castle Pines, after she lost two family members to pancreatic cancer. The organization is dedicated to supporting research and clinical care at CU Cancer Center. “The pancreatic cancer research and treatment taking place at CU Cancer Center is second to none, and it is a privilege to have Wings of Hope a focused part of the effort to raise awareness as well as funding for this incredibly important work,” Shul says. Maureen Shul and Colin Weekes COURTES Y OF WI NGS OF HOPE http://events.coloradocancercenter.org MARC BE RGMAN 19 C3: SPRING 2013 UNIVERSITY OF COLORADO DENVER SPRI NG 2013 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 Non-profit organization U.S. POSTAGE PAID Denver, CO Permit No. 831 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, Mary Lemma Photos: Glenn Asakawa, Marc Bergman, Patrick Campbell, Casey Cass, Marla Keown, 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 M E S S A G E Membership in the National Comprehensive Cancer Network (NCCN) allows CU Cancer Center to shape the standard of care W Anderson, ithin the sea of cancer research and treatment facilities are 67 cancer centers designated by the National Cancer Institute. Within those are 41 desig- Each set of these NCCN guidelines is overseen by a panel of 25 to 30 medical experts drawn from NCCN member institutions. Now, with CU Cancer Center’s NCCN membership, we will be nominating our experts to these panels and will have the opportunity to help shape these blueprints for how to treat cancer patients. We have always striven to provide today’s best cancer treatments in an effective, compassionate and ethical way. Now the research and treatments we develop and test at CU Cancer Center will influence how the thousands of independent cancer clinics around the country treat their patients. For example, experts in our worldrenowned bladder and lung cancer programs will contribute their knowledge of the evolving use of targeted treatments for these diseases; we will be helping to nated comprehensive cancer centers. And within those are 23 recognized as members of the National Comprehensive Cancer Network (NCCN). As of March 2013, the University of Colorado Cancer Center is one of these 23 elite NCCN institutions that also include MD Memorial Sloan-Kettering, FROM THE DIRECTOR DAN THEODORESCU, MD, PhD Harvard’s Dana-Farber, Johns Hopkins’ Kimmel Cancer Center and other similarly influential institutions. It’s not bad company. But the NCCN designation means more than the opportunity to rub elbows with the best cancer centers in the world. The NCCN Clinical Practice Guide lines in Oncology are a set of 58 collected “The research and treatments we develop and test at CU Cancer Center will influence how the thousands of independent cancer clinics around the country treat their patients.” recommendations for the prevention, detection and treatment of various types of cancer, used by oncologists of every stripe— radiation, surgical and medical—in the United States and abroad. Increasingly, the NCCN guidelines also play an important role in making insurance coverage and policy decisions and in evaluating the quality of cancer care hospitals provide. The hope is that by following these guidelines, patients throughout the University of Colorado Health system and indeed across the country will receive standardized care for their cancer diagnoses, based on the most current, evidence-based understanding of the diseases. drive the debate about screening for melanoma, breast, prostate and colorectal cancers; and we will be leading the acceptance of new drugs and new techniques to test for and combat cancers for which 10 years ago there were no treatments. In short, with NCCN membership, CU Cancer Center has taken an important step toward significantly contributing to how cancer medicine is practiced. It’s an exciting time in cancer research and the development of cancer care, and now with a NCCN designation we are at the forefront with the institutions that are leading the way. 20 WWW.COLORADOCANCERCENTER.ORG