title: Towards a unified model of RAF inhibitor resistance.
abstract: ATP-competitive RAF inhibitors elicit profound but often temporary antitumor responses in patients with BRAF-mutant melanoma. Analysis of tumor samples collected at the time of disease progression indicates that alterations within the extracellular signal-regulated kinase (ERK) pathway that result in reactivation of ERK signaling are present in most patients. Mutations in the phosphoinositide 3-kinase/AKT pathway that enhance the adaptive response to RAF inhibitors also contribute to RAF inhibitor resistance in a subset of patients.
authors.affiliation: 1Department of Medicine, 2Human Oncology and Pathogenesis Program, and 3Program in Molecular Pharmacology, Memorial Sloan-Kettering Cancer Center, New York, New York.
authors.forename: David B
authors.initials: DB
authors.lastname: Solit
authors.forename: Neal
authors.initials: N
authors.lastname: Rosen
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D048493:Proto-Oncogene Proteins B-raf; D048049:Extracellular Signal-Regulated MAP Kinases