Journal
CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY
Volume 96, Issue 3, Pages 385-398Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.critrevonc.2015.08.021
Keywords
BRAF mutations; BRAF inhibitors; MEK inhibitors; Melanoma; Resistance; Targeted therapy
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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 naive and resistant BRAF mutant melanoma. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
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