Gene mutations predict which lung cancers will respond to Iressa

Researchers from the Massachusetts General Hospital (MGH) Cancer Center have discovered a molecular marker that identifies lung cancer patients whose tumors will respond to treatment with the drug Iressa (gefitinib). Their findings, which will be published in the May 20 New England Journal of Medicine, are being released online today to coincide with the online release by Science of related research from Dana-Farber Cancer Institute.

"This discovery will help us significantly improve the treatment of many lung cancer patients and is also an important next step in the molecular targeting of cancer drugs," says Daniel Haber, MD, PhD, director of the MGH Cancer Center and senior author of the NEJM paper. "We're hopeful that what we have learned will eventually lead to more new drugs that will target tumor-specific mutations without affecting normal tissues."

Iressa was approved a year ago for the treatment of advanced non-small-cell lung cancer (NSCLC), a tumor that is particularly difficult to treat and is the leading cause of cancer deaths in the U.S. In a major clinical trial Iressa caused tumors to shrink significantly in only 13.6 percent of patients, but some of those responses were rapid and dramatic. As a result, the FDA approved the drug because there are no other treatment options for NSCLC patients for whom standard chemotherapy has failed.

Iressa acts by disabling the epidermal growth factor receptor (EGFR) on the surface of lung cancer cells, halting a sequence of signals that can lead to the uncontrolled growth characterizing a malignant tumor. In their search for an answer to why the drug worked so well for some NSCLC patients but was of no assistance to others, the MGH team screened tumor samples from MGH patients who participated in the Iressa clinical trial to search for mutations in the EGFR gene.

Initial analysis found mutations affecting the same area (the ATP cleft of the kinase domain) of the receptor prot

Contact: Sue McGreevey
Massachusetts General Hospital

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