title: Targeting the hepatocyte growth factor/c-Met signaling pathway in renal cell carcinoma.
abstract: The product of a proto-oncogene, the c-Met protein is a transmembrane receptor tyrosine kinase. Its only known ligand, hepatocyte growth factor/scatter factor, regulates cell growth, motility, migration, invasion, proliferation, and angiogenesis. Dysregulation of c-Met and hepatocyte growth factor have been observed in both clear cell and non-clear cell renal cell carcinomas (RCCs), although only papillary RCCs harbor activating mutations in the MET gene. In clear cell RCC, there is evidence of a direct link between loss of von Hippel-Lindau and up-regulation of c-Met. As in other cancers, high expression of c-Met correlates with worse outcomes in RCC. In vitro and in vivo preclinical RCC models demonstrate cancer control with small molecule and antibodies against c-Met. Given these findings, the c-Met pathway is a logical therapeutic target in RCC, and several agents are in clinical testing with early signs of efficacy.
authors.affiliation: Dana-Farber Cancer Institute, Dana 1230 Solid Tumor Oncology, Lank Center for Genitourinary Oncology, Boston, MA 02215, USA.
authors.forename: Lauren C
authors.initials: LC
authors.lastname: Harshman
authors.forename: Toni K
authors.initials: TK
authors.lastname: Choueiri
mesh_terms: D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D017228:Hepatocyte Growth Factor / Q000235:genetics* / Q000378:metabolism / Q000627:therapeutic use; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D058990:Molecular Targeted Therapy; D009154:Mutation; D000090063:Proto-Oncogene Mas; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics* / Q000378:metabolism / Q000627:therapeutic use; D015398:Signal Transduction
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met