Beyond BRAF: where next for melanoma therapy?

Br J Cancer. 2015 Jan 20;112(2):217-26. doi: 10.1038/bjc.2014.476. Epub 2014 Sep 2.


In recent years, melanoma has become a poster-child for the development of oncogene-directed targeted therapies. This approach, which has been exemplified by the development of small-molecule BRAF inhibitors and the BRAF/MEK inhibitor combination for BRAF-mutant melanoma, has brought new hope to patients. Despite these successes, treatment failure seems near inevitable in the majority of cases—even in individuals treated with the BRAF/MEK inhibitor doublet. In the current review, we discuss the future of combination strategies for patients with BRAF-mutant melanoma as well as the emerging therapeutic options for patients with NRAS-mutant and BRAF/NRAS-wild-type melanoma. We also outline some of the newest developments in the in-depth personalisation of therapy that should allow melanoma treatment to continue shaping the field precision cancer medicine.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Clinical Trials as Topic
  • Drug Resistance, Neoplasm / genetics
  • GTP Phosphohydrolases / genetics
  • Humans
  • Melanoma / drug therapy
  • Melanoma / genetics
  • Membrane Proteins / genetics
  • Molecular Targeted Therapy
  • Mutation, Missense
  • Proto-Oncogene Proteins B-raf / antagonists & inhibitors
  • Proto-Oncogene Proteins B-raf / genetics*
  • Skin Neoplasms / drug therapy
  • Skin Neoplasms / genetics


  • Antineoplastic Agents
  • Membrane Proteins
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • GTP Phosphohydrolases
  • NRAS protein, human