The Fight of a Lifetime

by Gabrielle Balzell
Photography by David Vernon/cancer cell photos courtesy of UICOMP

Some of today’s most promising cancer research is being conducted right here in Peoria.

In the year 2013, the “C” word still has the ability to make people cringe. Despite the many advances in research, prevention and treatment, cancer still accounts for one in every eight deaths worldwide—more than HIV/AIDS, tuberculosis and malaria combined. In the U.S., it’s the second leading cause of death, surpassed only by heart disease. The harsh reality is that half of all men and a third of all women in the U.S. will develop some type of cancer in their lifetime.

Last year alone, an estimated 1.64 million new cancer cases were diagnosed across the nation, nearly 66,000 of them in Illinois. Not only is this disease debilitating adults and children without discrimination, it’s costing a fortune while it wreaks its havoc. In 2007, the National Institutes of Health estimated these costs at a whopping $226.8 billion annually. And yet, a glimmer of hope shines within central Illinois.

With world-class hospitals, a renowned medical school, the St. Jude Midwest Affiliate and an extensive network of healthcare facilities, there’s no doubt that Peoria is the region’s leader in healthcare. Even as you read this, some of its most accomplished physicians, nurses and researchers are hard at work in labs, at bedsides and in the field leading the crusade against cancer. With access to a broad base of resources and talent, Peoria is home to some of the most innovative cancer research in the country—and the world—which someday soon might just stop the disease in its tracks.

On the Verge of a Breakthrough
At the University of Illinois College of Medicine at Peoria (UICOMP), Dr. Eleonora Zakharian is toiling away in a laboratory at the school’s new Cancer Research Center. Her goal: defining the role of transient receptor potential (TRP) ion channels in malignant cells—and determining how they can be used to fight cancer.

TRP ion channels are the sensors that reside on the surface of cells, both normal and cancerous, which allow cells to communicate with one another. When stimulated by specific compounds, they open up and allow certain elements to flow through them. Scientists believe they may actually play a protective role in cancer cells, as they contribute to intracellular levels of calcium, a crucial element that can signal cell proliferation or apoptosis (programmed cell death). In the not-so-distant future, researchers hope to stimulate these molecular pathways to allow in a drug that can signal malignant cells to die instead of multiply.

The problem is that these TRP ion channels only stay open for a certain amount of time before closing again. After the stimulus has been applied for some time, the cells become desensitized to it, causing the channels to close up, and ending any potential cancer-fighting drug’s ability to kill the malignant cells.

With funding from the National Institutes of Health, Dr. Zakharian hopes to resolve this problem by studying proteins from cells whose TRP ion channels can be activated by menthol. Already, she has a leg up on the process, as her team was the first to purify channel proteins from mammalian cells, allowing her to study them in artificial membranes to learn exactly how they respond to particular compounds. “[It] gives us the freedom to use different drugs, because we can test several compounds right in that purified system and define how they affect a single molecule, which you cannot do on the cells,” she explains. “So we know that if we apply one drug, that will activate it; if we apply another drug, that will inhibit it.”

This research is an important first step in a process that could someday yield an anti-cancer drug for clinical testing. At the very least, it promises to offer new insights into cancer treatment. “The clinical studies have to be supported by basic science,” she adds. “If we [know] what molecules can stop [cancer growth]… we will be able to provide information for the development of drugs that can really treat that. That will be a big, big help for the patients to fight against this terrible disease.”

Clinical Care Close to Home
And if Dr. Zakharian’s research ultimately leads to the production of a new cancer-fighting drug, it’s likely to be tested not far from her laboratory.

Founded in 1977 by Dr. Stephen Cullinan, Illinois CancerCare is one of the nation’s largest private oncology practices. Its 13 clinics scattered throughout central Illinois offer state-of-the-art treatment to cancer patients and serve as test sites where groundbreaking research occurs every day through a range of clinical trials that focus on everything from cancer prevention to treatment to symptom management. In fact, the organization’s Community Clinical Oncology Program (CCOP) happens to be one of the top enrollers for cancer clinical trials in the country.

The Alliance of Clinical Trials in Oncology recently ranked Illinois CancerCare’s CCOP ninth in the nation for treatment and trials that seek to prevent cancer or control its incidence. In addition, its 11-percent patient accrual rate is well above the four-percent national average and ahead of many nationally recognized programs. This is a testament to the quality at Illinois CancerCare, which is often the first or only site in the Midwest—or the nation—offering a particular clinical trial. “Our history of conducting clinical research shows that we have a proven track record,” explains Jamie Harper, clinical research supervisor at the center. “We see patients being referred to us from Mayo Clinic [and] MD Anderson… We get them from all across the country because we have these opportunities available that no one else in this region has.”

For local cancer patients, that means the opportunity to participate in national clinical trials—and potentially life-saving ones—right in their own community. “Instead of driving two-and-a-half or three hours to a big city to get treatment, they can drive 20 minutes and receive the same care, if not better,” she adds. “Having that high-quality research program available to the patients in their communities is something unique to us.”

Many of the more than 3,000 patients who have participated in the center’s clinical trials over the past three decades were among the first to benefit from drugs recently approved by the Food and Drug Administration. Illinois CancerCare was one of the only sites in the country to test enzalutamide, commonly sold under the name Xtandi, which is now approved to fight prostate cancer. Other successful trials include those for pertuzumab, often sold as Perjeta and used to combat breast cancer, and Cymbalta, a common antidepressant that was found to also reduce peripheral neuropathy, a painful side effect of certain types of chemotherapy. During the Cymbalta trial, Illinois CancerCare actually enrolled more patients than any other facility in the country.

Whether or not they result in FDA approval, each trial is a step closer to finding a cure and some relief for those afflicted. “If you look back over the last 10, 15, 20 years, we have an increasingly high standard for what we’re willing to accept in terms of quality of life,” explains Dr. Michele Rice, director of pharmacy and research. “There have been such advances in supportive care and targeted therapies that help people go about their normal lives as much as possible—so not just helping people be cured or stay alive as long as possible, but to help keep that quality of life… I think and I hope that that will continue to be the trend.”

Both Harper and Dr. Rice believe that targeted therapy—treatment which kills cancer cells while leaving healthy cells alone—is the future of cancer research, and something on which Illinois CancerCare will concentrate in the coming years. Additional clinical trials involving brain cancer will likely be in the future as well, thanks to Dr. Francois Geoffroy’s recent completion of the neuro-oncology fellowship at Duke University Medical Center. The only oncologist-hematologist in the state outside of Chicago and St. Louis to have completed the program, he can now bring the latest knowledge in the treatment of brain tumors back to central Illinois.

With between 90 and 150 clinical trials going on at any given time, the organization offers a dose of optimism to those who walk through its doors. “I think anytime we can provide a patient hope… that’s a successful trial,” Harper says. “That’s really what we strive for—giving our patients that sense of accomplishment, that sense that they’re fighting back… That’s really the driving force behind providing these opportunities.”

From Central Illinois to Central America
Instilling that sense of hope is just as critical in pediatric patients as it is in adults, and a number of local physicians have dedicated their lives to doing just that.

“No child should die in the dawn of life.” That was the belief of the late Danny Thomas, founder of St. Jude Children’s Research Hospital. Taking this message to heart, Drs. Pedro de Alarcon and Karen Fernandez, professors at UICOMP and hematologist-oncologists for the St. Jude Midwest Affiliate at Children’s Hospital of Illinois, are working tirelessly to ensure that all children have a chance to live a full life. Focusing their studies mostly in pediatric neuroblastoma (a type of cancer that develops from immature nerve cells), Hodgkin’s lymphoma and leukemia, they have been the driving force behind several pioneering studies through their collaboration with organizations such as the Children’s Oncology Group (COG).

Through one of these partnerships, Dr. de Alarcon was able to design and execute the first randomized clinical trial to test the treatment of opsoclonus-myoclonus—an extremely rare neurological disorder associated with neuroblastoma—and help develop three chemotherapy regimens that have become standard for children with Hodgkin’s lymphoma. He was also one of the creative minds behind the largest pediatric Hodgkin’s lymphoma trial ever conducted, which tested 1,700 children across the U.S. to determine the effectiveness of radiation in their treatment. Completed in 2009, the study found that in the majority of cases, radiation therapy made little difference in overall treatment—a finding which could change how the disease is treated and potentially lower patients’ long-term toxicity rates.

While chemotherapy and radiation can treat many cases of cancer, their long-term side effects—which may not appear for decades—can sometimes be more deadly than the disease itself. In addition to a slew of infections, patients can suffer organ and nerve damage, cardiovascular disease, thyroid problems and other ailments due to toxicity. While adult cancer survivors may never experience these effects, pediatric survivors will most likely experience them at middle age. This has been a key motivator behind Dr. Fernandez’ work to determine how children’s Hodgkin’s lymphoma treatment protocols can be altered to minimize long-term toxicity, extend patients’ lives and improve their quality.

Drs. Fernandez and de Alarcon have also reevaluated the Hodgkin’s lymphoma treatment protocols of adolescent patients, finding that most adolescents do just as well with pediatric treatment as they do with adult treatment. This, again, may change the way this age group is treated in the future. Because pediatric treatment involves half as many chemotherapy cycles and offers a 15-percent higher survival rate over adult treatment protocols, more children could be saved and suffer fewer long-term side effects.

Komen for the Cure

Founded in memory of the Peoria native, Susan G. Komen for the Cure has become a global leader in the fight against breast cancer, investing more than $1 billion in the cause since its inception. Established in 1982 with a single $28,000 grant, today the organization manages more than 600 active research grants totaling nearly $300 million. Since 1988, 62 grants have been issued in Illinois—totaling more than $16 million—with 16 active grants that invest nearly $6.5 million in breast cancer research.

Peoria is also the site of the second oldest Race for the Cure, which raises approximately $1 million each year for breast cancer research, education, screening and treatment. With 75 percent of all local proceeds staying in central Illinois, the Memorial Affiliate has awarded more than $9 million—and over $600,000 last year alone—to regional agencies, primarily through its community health grants, which support education, screening and treatment for mostly low-income and uninsured/underinsured women. These grants have helped fund the initiatives of several area organizations, including Illinois CancerCare, Hult Center for Healthy Living, Methodist Medical Center Foundation and OSF Saint Francis Medical Center Foundation.

On the international front, Komen has launched a breast cancer outreach initiative in Latin America through more than $2 million in grants from the Caterpillar Foundation. This investment is being used to improve education, screening and early detection outcomes in Mexico, Brazil and Panama, where breast cancer mortality rates are higher than in more developed countries.

But wherever grants are being used, Gina Morss-Fischer, the Memorial Affiliate’s development director, stresses that local efforts make a global impact. “Whether it’s being done in our backyard, at Wash U in St. Louis or [John Hopkins University], wherever it’s taking place around the country and beyond, local dollars have had an impact. Local efforts—volunteer efforts—have made a difference. Because that research portfolio would not be possible without the support of people all across the country, not the least of which is right here in Suzy’s hometown.” For more information, visit komenmemorial.org or call (309) 691-6906.

Translating their expertise across borders, the physicians’ research in Central America has also yielded new insights. Since 2004, Drs. Fernandez and de Alarcon have been members of a team conducting a study of children in developing countries with low and intermediate-risk Hodgkin’s lymphoma. Because of the lack of funding and supportive facilities in these countries, they’ve been forced to tweak the standard treatment protocols, with intriguing results. Most of the patients studied responded to chemotherapy alone—and to a lower dose than what’s normally used in the U.S. This data could initiate new protocols back in the states, with tremendous cost savings and less toxic ways to treat these diseases, including lower doses of chemotherapy and the elimination of radiation therapy and bone marrow transplants except when absolutely necessary.

Recently named the Jim and Katie Owens - OSF Professor of Hematology Oncology, Dr. Fernandez is now bringing UICOMP, Children’s Hospital of Illinois and St. Jude Children’s Research Hospital together for a collaborative investigation involving pediatric patients in Guatemala with acute lymphoblastic leukemia, the most common childhood cancer. For the last two years, doctors have been collecting blood samples from these patients, as well as their parents and siblings, and conducting analyses to determine which gene makes children of Hispanic descent more susceptible to the disease. This research could provide vital information for the development of targeted therapies, more economical treatments and diagnostic tests, as their studies of Hodgkin’s lymphoma have done.

With St. Jude having embarked on a $65-million Pediatric Cancer Genome Project in 2010, Drs. Fernandez and de Alarcon have recently been focusing their attention on proteomics, or protein analysis. They are currently collecting plasma samples from all over the country to determine if protein signatures can serve as accurate predictors of who will respond well to typical treatment for pediatric Hodgkin’s lymphoma patients. If successful, their findings could save precious time and allow doctors to use alternative treatment in patients whose signatures suggest they won’t respond well to standard protocols. “That’s why we do genomics; that’s why we do proteomics,” Dr. de Alarcon stresses. “It’s to find out what makes you as an individual different from the next one—and how we can tailor what we know that’s effective… specifically for you. We’re not there yet… but that’s why [these projects are] so important.”

Continuing the Fight
While cancer was once a death sentence, many of today’s cancer patients go on to live long, fulfilling lives. Through the unrelenting efforts of physicians and researchers past and present, great progress has been made in the fight against cancer, but a sustained focus is needed to make it through the final round. “The success we have today is the product of the research of other people in the past,” Dr. Fernandez explains. “We have to continue to do that in order to see the same things—or better things—in 10 or 15 years ahead.”

Though its expiration date is not yet known, cancer’s reign of death and devastation continues to inch closer to its end. Attesting to that fact are approximately 13.7 million cancer survivors in the U.S.—and nearly 550,000 in Illinois alone—a number expected to grow to nearly 18 million by 2022. Peoria’s premier healthcare centers—and the discoveries being made inside them—may very well contain the key to a cure once and for all. iBi

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