Targeting oncogenic BRAF and aberrant MAPK activation in the treatment of cutaneous melanoma

Crit Rev Oncol Hematol. 2015 Dec;96(3):385-98. doi: 10.1016/j.critrevonc.2015.08.021. Epub 2015 Aug 28.

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.

Keywords: BRAF inhibitors; BRAF mutations; MEK inhibitors; Melanoma; Resistance; Targeted therapy.

Publication types

  • Review

MeSH terms

  • Humans
  • MAP Kinase Signaling System / drug effects*
  • Melanoma / drug therapy*
  • Protein Kinase Inhibitors / therapeutic use*
  • Proto-Oncogene Proteins B-raf / antagonists & inhibitors*
  • Skin Neoplasms

Substances

  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins B-raf

Supplementary concepts

  • Melanoma, Cutaneous Malignant