Therapeutic potential of c-MET inhibitors: background and clinical data

Author(s): Shawna Leslie Organ, J Rafael Sierra,Ming-Sound Tsao

In the last 30 years, since the discovery of the HGFR (also known as c-MET), much has been learned about its roles in a broad spectrum of cellular phenotypes, including mitogenesis, morphogenesis, angiogenesis and invasiveness. While these phenotypes are tightly regulated during embryogenesis and in adulthood processes, such as wound healing and liver regeneration, they can be responsible for tumor initiation and progression when c-MET is aberrantly activated by mutation, gene amplification and/or protein overexpression. As such, both c-MET and HGF have several targeted inhibitors currently in clinical trials. This manuscript provides an overview of the c-MET signaling pathway, including its role in the development of cancers, and presents data that support this pathway as a relevant target for personalized cancer treatment.