Working Toward Personalized Medicine

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). However, 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 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. A finding that was unexpected was that patients whose tumor mutations were associated with better responses to imatinib did worse on sunitinib, and vice versa.

The study was led by Michael C. Heinrich, M.D., professor of medicine (hematology and medical oncology) in the OHSU School of Medicine and a member of the OHSU Cancer Institute, and colleagues. He presented the results of the study at the annual meeting of the American Society of Clinical Oncology in Atlanta (GA) in June 2006.

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, said Dr. Heinrich. With certain genetic mutations, some drugs work better than others. This is about personalized medicine and how to get there. What we're finding out about cancer is that when choosing a therapy, one size doesn't fit all. This is a study about GIST 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.



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