title: B-Raf and the inhibitors: from bench to bedside.
abstract: The B-Raf protein is a key signaling molecule in the mitogen activated protein kinase (MAPK) signaling pathway and has been implicated in the pathogenesis of a variety of cancers. An important V600E mutation has been identified and can cause constitutive B-Raf activation. Recent studies have evaluated a variety of small molecule inhibitors targeting B-Raf, including PLX4032/vemurafenib, dabrafenib, LGX818, GDC0879, XL281, ARQ736, PLX3603 (RO5212054), and RAF265. Therapeutic resistance has been identified and various mechanisms described. This review also discussed the current understanding of B-Raf signaling mechanism, methods of mutation detection, treatment strategies as well as potential methods of overcoming therapeutic resistance.
authors.affiliation: Department of Pathology, Westchester Medical Center and New York Medical College, Valhalla, NY 10595, USA.
authors.forename: Tiangui
authors.initials: T
authors.lastname: Huang
authors.forename: Michael
authors.initials: M
authors.lastname: Karsy
authors.forename: Jian
authors.initials: J
authors.lastname: Zhuge
authors.forename: Minghao
authors.initials: M
authors.lastname: Zhong
authors.forename: Delong
authors.initials: D
authors.lastname: Liu
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
chemical_list: D047428:Protein Kinase Inhibitors; D048493:Proto-Oncogene Proteins B-raf