From rxpgnews.com

Cancer
Genetic Mutation in Patients with GIST Predicts Response to Imatinib
By American Society of Clinical Oncology
May 18, 2005, 01:45

A new study shows that patients with gastrointestinal stromal tumors (GIST) who have a particular genetic mutation are more likely to respond to imatinib (Gleevec) than those without the mutation.

GIST, a rare cancer of the GI tract, is commonly treated with imatinib. Imatinib works by inhibiting a receptor protein called KIT, which is expressed in a mutant form in GIST. The mutant KIT fuels tumor growth by signaling cancer cells to keep growing. In approximately 90% of patients, KIT is activated by a mutation of the KIT gene in tumor cells. The majority of GIST patients have dramatic clinical improvement in their disease (tumor shrinkage) after beginning treatment with imatinib. However, more than half of patients develop resistance to the therapy and experience disease progression after about two years.

Researchers performed a genetic analysis of tissue samples from 324 GIST patients obtained before they began treatment with imatinib, and correlated the findings with patient outcome.

Patients whose tumors expressed a mutation in a certain portion ("exon 11") of the KIT gene fared better than those with mutations in exon 9 of KIT or those with no KIT mutations. More patients with a KIT exon 11 mutation (67%) responded to imatinib than those with the KIT exon 9 mutation (40%) or no mutation (39%). Patients with the KIT exon 11 mutation also responded to imatinib for a longer period (576 days) than those with the KIT exon 9 mutation (308 days).

"Increasingly, there will be more drugs like imatinib that are very specific in their action, and patients' responses to them will be dictated by their individual tumor biology," said Michael C. Heinrich, MD, Professor of Medicine at the Oregon Health and Science University Cancer Institute, and lead author of the study. "Performing genetic analyses of patients' tumors will be useful for doctors in determining how patients should be treated."

Future studies will evaluate the use of imatinib in combination with other agents to treat GIST patients. "We have a powerful tool in imatinib," concluded Dr. Heinrich. " However, we need to find ways to use the therapy so it doesn't just shrink tumors, but totally eliminates the cancer cells so the tumors don't come back."


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