Treatment of NRAS-mutant melanoma

Curr Treat Options Oncol. 2015 Apr;16(4):15. doi: 10.1007/s11864-015-0330-z.


NRAS mutations in codons 12, 13, and 61 arise in 15-20 % of all melanomas. These alterations have been associated with aggressive clinical behavior and a poor prognosis. Until recently, there has been a paucity of promising genetically targeted therapy approaches for NRAS-mutant melanoma (and RAS-mutant malignancies in general). MEK inhibitors, particularly binimetinib, have shown activity in this cohort. Based on pre-clinical and early clinical studies, combining MEK inhibitors with agents inhibiting the cell cycling and the PI3K-AKT pathway appears to provide additional benefit. In particular, a strategy of MEK inhibition and CDK4/6 inhibition is likely to be a viable treatment option in the future, and is the most promising genetically targeted treatment strategy for NRAS-mutant melanoma developed to date. In addition, immune-based therapies have shown increasing activity in advanced melanoma and may be particularly effective in those with NRAS mutations. Combination strategies of immune and targeted therapies may also play a role in the future although clinical trials testing these approaches are in early stages.

Publication types

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

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • GTP Phosphohydrolases / genetics*
  • Humans
  • Immunotherapy*
  • Melanoma / drug therapy*
  • Melanoma / genetics*
  • Melanoma / pathology
  • Membrane Proteins / genetics*
  • Mutation*


  • Antineoplastic Agents
  • Membrane Proteins
  • GTP Phosphohydrolases
  • NRAS protein, human