C-MET as a novel target for the treatment of renal cell carcinoma

Abstract

Germline mutations in c-met proto-oncogene contribute to development of papillary renal carcinomas. C-met encodes a receptor tyrosine kinase, and it controls genetic programs leading to cell growth, invasion, and protection from apoptosis. Hepatocyte growth factor/scatter factor (HGF/SF) is identified as c-met ligand. Met is expressed in epithelial cells of many organs, both during embryogenesis and adulthood, and its function is essential for embryo development. Dysregulation of MET and HGF/SF signaling has emerged as a crucial feature of many human malignancies. HGF/SF and/or Met over- or misexpression often correlates with poor prognosis. C-met can be activated by multiple ways, either by its overexpression/structural alterations or HGF-dependent or HGF-independent mechanisms or by interacting with other receptor families. Based on these, different strategies were developed to target and inhibit c-met signaling.