Molecular Marker Predicts Patients Most Likely to Benefit Longest from Two Popular Cancer Drugs

Johns Hopkins scientists and collaborators have identified a molecular marker called "Mig6" (mitogen-inducible gene 6) that appears to accurately predict longer survival -- up to two years -- among patients prescribed two of the most widely used drugs in a class of anticancer agents called EGFR inhibitors. The U.S. Food and Drug Administration-approved drugs, gefitinib (Iressa) and erlotinib (Tarceva), are prescribed for lung and pancreatic cancer patients, but only a few who have mutations in the EGFR gene usually benefit with a prolonged reduction of tumor size. The two drugs block the gene's ramped-up protein production, but patients' responses to the drug vary widely – from no survival benefit to several years. The average is several months. "Clinicians have had no reliable method for distinguishing patients who are not likely to respond to EGFR inhibitors and those who will respond very well," says David Sidransky, M.D., professor of otolaryngology, oncology, pathology, urology, and genetics at Johns Hopkins. Looking at the precise level of protein production from the EGFR gene alone in specific patients was not proven to be a good indicator of patients' response to EGFR-blocking drugs, but the presence or absence of Mig6 might be, he adds. In a preliminary study,publishe on July 31, 2013 in the online open-access journal, PLOS ONE, the Johns Hopkins scientists found the genetic marker in a series of experiments that began with laboratory-derived lung and head and neck cancer cell lines resistant to EGFR-inhibitor drugs. In the cell lines, the team found very high levels of protein production from the Mig6 gene -- up to three times the level in sensitive cell lines. Mig6 is one of the molecules that controls the activity of the EGFR protein.
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