title: HGF/c-MET targeted therapeutics: novel strategies for cancer medicine.
abstract: The hepatocyte growth factor/mesenchymal-epithelial transition factor (HGF/c-MET) receptor tyrosine kinase (RTK) pathway plays a pleotropic role in cell proliferation, migration, invasion, angiogenesis and survival. Although it has critical physiological functions in embryonic development and tissue repair, this signaling cascade is frequently deregulated in a wide range of tumors. Aberrant HGF/c-MET signaling, driven by various mechanisms, including constitutive activation and over-expression, has multifunctional effects in oncogenesis and is implicated in the acquisition of an aggressive phenotype with metastatic potential. The central role of c-MET activity in cancer progression, as well as disparities between quiescent HGF/c-MET signaling in normal tissue and overexpression in tumor may provide a degree of tumor selectivity for therapeutic intervention, making HGF or c-MET inhibition an attractive proposition in oncology. This review focuses on the underlying oncogenic role of aberrant HGF/c-MET signaling in malignant progression, as well as recent preclinical and clinical data on the different strategies employed in inhibiting HGF/c-MET function.
authors.affiliation: Royal Marsden NHS Foundation Trust and The Institute of Cancer Research Downs Road, Sutton, Surrey, United Kingdom.
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Yap
authors.forename: Shahneen K
authors.initials: SK
authors.lastname: Sandhu
authors.forename: Salma M
authors.initials: SM
authors.lastname: Alam
authors.forename: Johann S
authors.initials: JS
authors.lastname: de Bono
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017228:Hepatocyte Growth Factor / Q000037:antagonists & inhibitors* / Q000502:physiology; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000209:etiology; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors* / Q000502:physiology; D015398:Signal Transduction
chemical_list: D000970:Antineoplastic Agents; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met