title: Targeting RAF kinases for cancer therapy: BRAF-mutated melanoma and beyond.
abstract: The identification of mutationally activated BRAF in many cancers altered our conception of the part played by the RAF family of protein kinases in oncogenesis. In this Review, we describe the development of BRAF inhibitors and the results that have emerged from their analysis in both the laboratory and the clinic. We discuss the spectrum of RAF mutations in human cancer and the complex interplay between the tissue of origin and the response to RAF inhibition. Finally, we enumerate mechanisms of resistance to BRAF inhibition that have been characterized and postulate how strategies of RAF pathway inhibition may be extended in scope to benefit not only the thousands of patients who are diagnosed annually with BRAF-mutated metastatic melanoma but also the larger patient population with malignancies harbouring mutationally activated RAF genes that are ineffectively treated with the current generation of BRAF kinase inhibitors.
authors: 1] Helen Diller Family Comprehensive Cancer Center and Department of Cell and Molecular Pharmacology, University of California, San Francisco, California 94158, USA. [2].
authors: Matthew
authors: M
authors: Holderfield
authors: 1] Helen Diller Family Comprehensive Cancer Center and Department of Cell and Molecular Pharmacology, University of California, San Francisco, California 94158, USA. [2].
authors: Marian M
authors: MM
authors: Deuker
authors: Helen Diller Family Comprehensive Cancer Center and Department of Cell and Molecular Pharmacology, University of California, San Francisco, California 94158, USA.
authors: Frank
authors: F
authors: McCormick
authors: Helen Diller Family Comprehensive Cancer Center and Department of Cell and Molecular Pharmacology, University of California, San Francisco, California 94158, USA.
authors: Martin
authors: M
authors: McMahon
mesh_terms: D000818:Animals; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics
chemical_list: D047428:Protein Kinase Inhibitors; D048493:Proto-Oncogene Proteins B-raf