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OHSU Cancer Institute Study Points To Future Of Personalized Medicine

When choosing a cancer treatment, one therapy does not fit all

Targeted therapies that attack tumors at the molecular level are increasingly the treatment of choice for cancer patients. But future therapies are likely to be even more individually tailored, with drugs and dosages determined by the nature of the patient's tumor.   

Scientists at the Oregon Health & Science University Cancer Institute and elsewhere have discovered that patients responded differently to the targeted therapy Sunitinib (Sutent) depending on the type of genetic abnormality in their cancer.   

The study was led by Michael C. Heinrich, M.D., professor of medicine (hematology and medical oncology) in the OHSU School of Medicine and the Portland Veterans Affairs Medical Center, and a member of the OHSU Cancer Institute. He will present results of the study on June 3 at the annual meeting of the American Society of Clinical Oncology in Atlanta, Ga.   

 "This is about personalized medicine and how to get there," Heinrich said. "What we're finding out about cancer is that when choosing a therapy, one size doesn't fit all."   

Imatinib (Gleevec), a drug originally developed at the OHSU Cancer Institute in collaboration with scientists at Novartis, was the first drug to demonstrate that molecular therapy works. Initially used to treat patients with chronic myelogenous leukemia, it has also proved successful in treating a rare stomach cancer called gastrointestinal stromal tumor (GIST). But imatinib doesn't work for every GIST patient, and even when it does work, many GIST patients develop resistance to it.   

Like imatinib, the oral drug Sunitinib is a targeted therapy, and it helps many GIST patients whose tumors are resistant to imatinib. Sunitinib interferes with a type of cellular protein known as a tyrosine kinase. It acts in two ways - helping to shrink tumors and to keep them from growing new blood vessels. In January, 2006 the U.S. Food and Drug Administration approved Suntinib for the treatment of imatinib-resistant GIST.   

The study examined tumors in 97 GIST patients who were taking Sunitnib during Phase I/II clinical trials. It also assessed the relationship between the effectiveness of the drug and the the type of mutations present in a patient's tumor. All patients experienced clinical benefit from the drug, but the benefit was significantly influenced by the nature of the abnormality.   

 "As we learn what's broken, we are learning new treatments to go after what's broken - what's driving the growth of the tumor," Heinrich said. "With certain genetic mutations, some drugs work better than others."   

One finding was unexpected: Patients whose tumor mutations were associated with better responses to imatinib did worse on sunitinib, and vice versa.   

The study has broad implications. "This is a study about GIST," Heinrich said, "but the big picture story is that in the future, when you are diagnosed with cancer, your physician will make sure the tumor is tested for specific gene mutations, and we will select your therapy based on what's wrong."   

Henrich will also co-chair a satellite symposium on targeted therapies on June 2. In addition, Heinrich and Christopher L. Corless, M.D., Ph.D., professor and vice chairman for research in the Department of Pathology, OHSU School of Medicine, and member of the OHSU Cancer Institute will participate in two "Meet the Professor" sessions on June 3 and June 5 titled "Technology Primer for Oncologists: Cell Signaling Pathways and Proliferation."   

In addition to Heinrich and Corless, collaborators in the study are Robert G. Maki, M.D., Ph.D., and Cristina R. Antonescu, M.D., Memorial Sloan-Kettering Cancer Center; J.A. Fletcher, M.D., and Christopher D.M. Fletcher, M.D., M.B., Brigham & Women's Hospital; Xianming Huang, Ph.D., University of Texas Southwestern Medical Center; Charles M. Baum, M.D., Pfizer, Inc.; and George D. Demetri, M.D., Dana-Farber Cancer Institute.

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