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Pathways to Discovery: Summer 2013

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Special Series: Personalized Medicine
The UCCCC is transforming the future of medicine by using genetic, social, and environmental factors to predict cancer risk and customize prevention and treatment strategies for our patients. In this installment of a special series on personalized medicine, we take a closer look at how the exciting field of pharmacogenomics is leading to safer and more effective cancer care. 

Pharmacogenomics Employs Genetic Information to Individualize Cancer Therapy 

Why drugs are effective for some individuals but not others is still largely a medical mystery, but genetics are believed to play an important role. In the 1970s, scientists began to analyze variations in one or a few genes to predict drug sensitivity. Following the explosion of genomic technology in the early 2000s, scientists expanded their search to the entire genome, opening up countless new possibilities.

This study of how a patient’s genetic makeup influences drug response, known as pharmacogenomics, is a pillar of personalized medicine.

“Looking at the whole genome allows us to determine which genetic signals are influencing drug response, as well as predict which patients will experience a severe side effect,” said R. Stephanie Huang, PhD, assistant professor of medicine. “Instead of the one-size-fits-all approach, we can use genetic information to optimize the timing of treatment and maximize the value of therapy.”

The University of Chicago Medicine Comprehensive Cancer Center (UCCCC) leads the emerging field of pharmacogenomics research, serving as the host institution for the National Institutes of Health-funded Pharmacogenomics of Anticancer Agents Research (PAAR) Group since 2000.

Principal investigators include M. Eileen Dolan, PhD, professor of medicine, Nancy Cox, PhD, professor of medicine, and Mark Ratain, MD, the Leon O. Jacobson Professor of Medicine and UCCCC associate director for clinical sciences. The research group brings together multidisciplinary expertise in pharmacology, genetics, and hematology/ oncology to discover how genetic differences impact the response to anticancer agents.

“Our program is strong because it runs the gamut from early discovery work to clinical implementation,” aid Dr. Dolan. “Not many groups can do that.”

To study the genetic interactions caused by many commonly used chemotherapy drugs, Dr. Dolan’s laboratory created cell-based models. Using cells from related individuals in 34 different families, they were able to show that some families are more sensitive to chemotherapies than others. This model system allows researchers to determine what percent of the variation in drug sensitivity is due to genetics.

In another study, Drs. Huang, Dolan and colleagues used a similar method to identify genetic markers that predict treatment outcomes in patients with ovarian cancer. They discovered a genetic variant in the NRG3 gene associated with a 17-month difference in survival outcomes for ovarian cancer patients treated with carboplatin, a commonly used chemotherapy. The NRG3 gene had not been previously associated with cancer nor with drug response.

Although such studies are generating many publications in the medical literature, more work is needed to incorporate this new information into clinical practice. The University of Chicago Center for Personalized Therapeutics is undertaking this task through its 1,200 Patients Project. Led by Peter O’Donnell, MD, assistant professor of medicine, the study is incorporating genetic information into routine clinical practice to help physicians prescribe the most effective medications with the fewest side effects.

Dr. Dolan said, “Oncologists need to be able to determine up-front if patients are responders or non-responders because it’s really important to switch their treatment early to avoid wasting time with an ineffective therapy that could have dangerous side effects.”

The UCCCC incorporates pharmacogenomics into more clinical trials than any other Cancer Center and already uses genetics to guide clinical practice. These unique strengths in pharmacogenomics research position the UCCCC as a leader in personalized medicine.