title: Progress in cancer therapy targeting c-Met signaling pathway.
abstract: A primary hurdle in developing anticancer therapeutics is to selectively target cancer cells while sparing normal tissues. Oncogenic protein kinases represent a class of biologically important targets for cancer intervention. Among them, c-Met is a receptor tyrosine kinase (RTK) that has low activity in normal tissues but is dysregulated in many tumor types. The c-Met is the prototype member of a subfamily of RTKs, which includes Ron, which is structurally distinct from other RTK families. It is the only known high-affinity receptor for hepatocyte growth factor, also known as scatter factor. HGF and c-Met are both required for normal mammalian development. In adults, both are widely expressed in a variety of tissues; however, their expression is normally very low and is involved mainly in tissue damage, repair and regeneration. The results of in vitro and in vivo experiments have shown that this receptor-growth factor pair is involved in multiple physiologic cellular responses, including cell proliferation, survival, differentiation, motility, and invasion. Here, as well as presenting the biological aspects of c-Met signaling regulation, we consider recent findings that have provided new knowledge at the molecular, cellular, and animal study. Also, we describe how the c-Met pathway is tuned by the functional cooperation between various signal transducers. We then discuss the progress in the development of agents that target the c-Met pathway, with an emphasis on small molecules of c-Met kinase inhibitors. Finally, we provide our perspective in terms of possible future trends and limitation in this field.
authors.affiliation: Department of Biomedical Sciences, College of Medicine, Inha University, Incheon, 400-712, Korea.
authors.forename: Kyung Hee
authors.initials: KH
authors.lastname: Jung
authors.forename: Byung Hee
authors.initials: BH
authors.lastname: Park
authors.forename: Soon-Sun
authors.initials: SS
authors.lastname: Hong
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002986:Clinical Trials as Topic; D055808:Drug Discovery; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors* / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D019859:Proto-Oncogene Proteins c-met