Targeted therapies for cutaneous melanoma

Hematol Oncol Clin North Am. 2014 Jun;28(3):491-505. doi: 10.1016/j.hoc.2014.02.003. Epub 2014 Apr 3.


Melanoma is resistant to cytotoxic therapy, and treatment options for advanced disease have been limited historically. However, improved understanding of melanoma driver mutations, particularly those involving the mitogen-activated protein kinase pathway, has led to the development of targeted therapies that are effective in this previously treatment-refractory disease. In cutaneous melanomas with BRAF V600 mutations the selective RAF inhibitors, vemurafenib and dabrafenib, and the MEK inhibitor, trametinib, have demonstrated survival benefits. Early signals of efficacy have also been demonstrated with MEK inhibitors in melanomas with NRAS mutations, and KIT inhibitors offer promise in melanomas driven through activation of their target receptor.

Keywords: BRAF; MAPK signaling; MEK; Melanoma; NRAS; Targeted therapy.

Publication types

  • Review

MeSH terms

  • Humans
  • Imidazoles / therapeutic use
  • Indoles / therapeutic use
  • Melanoma / drug therapy*
  • Melanoma / genetics
  • Molecular Targeted Therapy / methods*
  • Mutation
  • Oximes / therapeutic use
  • Protein Kinase Inhibitors / therapeutic use*
  • Proto-Oncogene Proteins B-raf / antagonists & inhibitors
  • Proto-Oncogene Proteins B-raf / genetics
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / genetics
  • Sulfonamides / therapeutic use
  • Survival Analysis
  • Vemurafenib


  • Imidazoles
  • Indoles
  • Oximes
  • Protein Kinase Inhibitors
  • Sulfonamides
  • Vemurafenib
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • dabrafenib