title: Targeting the hepatocyte growth factor-cMET axis in cancer therapy.
abstract: The hepatocyte growth factor (HGF) and its receptor, the transmembrane tyrosine kinase cMET, promote cell proliferation, survival, motility, and invasion as well as morphogenic changes that stimulate tissue repair and regeneration in normal cells but can be co-opted during tumor growth. MET overexpression, with or without gene amplification, has been reported in a variety of human cancers, including breast, lung, and GI malignancies. Furthermore, high levels of HGF and/or cMET correlate with poor prognosis in several tumor types, including breast, ovarian, cervical, gastric, head and neck, and non-small-cell lung cancers. Gene amplification and protein overexpression of cMET drive resistance to epidermal growth factor receptor family inhibitors, both in preclinical models and in patients. It is increasingly apparent that the HGF-cMET axis signaling network is complex, and rational combinatorial therapy is needed for optimal clinical efficacy. Better understanding of HGF-cMET axis signaling and the mechanism of action of HGF-cMET inhibitors, along with the identification of biomarkers of response and resistance, will lead to more effective targeting of this pathway for cancer therapy.
authors.affiliation: Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Box 432, Houston, TX 77030-4009, USA. gblumens@mdanderson.org
authors.forename: George R
authors.initials: GR
authors.lastname: Blumenschein
authors.forename: Gordon B
authors.initials: GB
authors.lastname: Mills
authors.forename: Ana M
authors.initials: AM
authors.lastname: Gonzalez-Angulo
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D018579:Patient Selection; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D019859:Proto-Oncogene Proteins c-met