Scientists at Johns Hopkins, Baltimore, have identified a molecular marker called “Mig 6” that appears to accurately predict longer survival—up to 2 years—among patients prescribed two of the most widely used drugs in a class of anticancer agents called EGFR inhibitors.
The FDA-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’ response to the drug varies 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, MD, 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 Mig 6 might be, he adds.
In a preliminary study, described July 31 in the online 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 Mig 6 gene—up to three times the level in sensitive cell lines. Mig 6 is one of the molecules that controls the activity of the EGFR protein.
“In the first set of experiments, we found that higher levels of Mig 6 occur often in cells that don’t respond to EGFR inhibitors,” Sidransky says. “Most tumors are known to have high Mig 6 levels and are not expected to respond to EGFR inhibitors.
“The beauty of this finding is that it’s simple,” Sidransky adds. “We’re looking for tumors with low levels of Mig 6 to predict clinical benefit, and there aren’t many of them.”
Sidransky’s team expects to license the Mig 6 marker to a biotechnology or pharmaceutical company and conduct further tests in larger groups of patients.
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[Source: Johns Hopkins]