title: Targeting oncogenic BRAF and aberrant MAPK activation in the treatment of cutaneous melanoma.
abstract: BRAF and MEK inhibitors, alone or in combination, are highly active in the 40% of patients with BRAF mutant metastatic melanoma. Despite this activity resistance often develops in patients treated with these agents. This review summarises the biology of the mitogen activated protein kinase (MAPK) pathway, with particular reference to the effects of BRAF and MEK inhibitors in BRAF mutant melanoma. The clinical and molecular predictors of response and mechanisms of resistance are discussed in detail along with the biological rationale and evidence for future treatment strategies in both MAPK inhibitor naïve and resistant BRAF mutant melanoma.
authors.affiliation: Departments of Medical Oncology, Crown Princess Mary Cancer Centre, Westmead Hospital, Sydney, New South Wales, Australia; Centre for Cancer Research, Westmead Millennium Institute, Westmead, New South Wales, Australia; Melanoma Institute Australia, Sydney, New South Wales, Australia; The Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia. Electronic address: matteo.carlino@sydney.edu.au.
authors.forename: Matteo S
authors.initials: MS
authors.lastname: Carlino
authors.affiliation: Melanoma Institute Australia, Sydney, New South Wales, Australia; The Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia; The Mater Hospital, North Sydney, New South Wales, Australia.
authors.forename: Georgina V
authors.initials: GV
authors.lastname: Long
authors.affiliation: Departments of Medical Oncology, Crown Princess Mary Cancer Centre, Westmead Hospital, Sydney, New South Wales, Australia; Centre for Cancer Research, Westmead Millennium Institute, Westmead, New South Wales, Australia; Melanoma Institute Australia, Sydney, New South Wales, Australia; Faculty of Medicine and Health Science, Macquarie University, New South Wales, Australia.
authors.forename: Richard F
authors.initials: RF
authors.lastname: Kefford
authors.affiliation: Centre for Cancer Research, Westmead Millennium Institute, Westmead, New South Wales, Australia; Melanoma Institute Australia, Sydney, New South Wales, Australia; Faculty of Medicine and Health Science, Macquarie University, New South Wales, Australia.
authors.forename: Helen
authors.initials: H
authors.lastname: Rizos
mesh_terms: D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008545:Melanoma / Q000188:drug therapy*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors*; D012878:Skin Neoplasms; D000096142:Cutaneous Malignant Melanoma
chemical_list: D047428:Protein Kinase Inhibitors; D048493:Proto-Oncogene Proteins B-raf
keywords: BRAF inhibitors; BRAF mutations; MEK inhibitors; Melanoma; Resistance; Targeted therapy