MET is a receptor, like EGFR, that receives signals from the environment and passes them on to the interior of the cell. When MET is activated, it signals other pathways, including PI3K/Akt and Ras, which results in cell growth and other cellular responses. Mutations and amplifications in the gene for MET have been identified in several types of cancer (56). In addition, MET amplification has been implicated as a mechanism by which cancer cells acquire resistance to EGFR inhibitors (11).
Screening patients for MET amplification may help identify patients who may be resistant to EGFR inhibitors and likely to benefit from treatment with a MET inhibitor.
A study performed in NSCLC cells found that MET-amplified cancer cells are susceptible to growth inhibition by drugs called MET inhibitors (57). In addition, additional studies in cell culture and mice have shown that MET-amplified cancer cells of various types are extremely susceptible to treatment with MET inhibitors (58, 59). Several MET inhibitors that either target MET specifically (called selective inhibitors) or MET along with other proteins (called multiple target inhibitors) have been developed. Examples of selective MET inhibitors include ARQ-197, PF-2341066, SGX523, and PHA-665752. An example of a multiple-target MET inhibitor is XL880, which inhibits both MET and another receptor called vascular endothelial growth factor receptor (VEGFR). Most of these MET inhibitors are still in early phase I clinical trials to determine their safety.