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Review
. 2015 Apr;16(4):15.
doi: 10.1007/s11864-015-0330-z.

Treatment of NRAS-mutant melanoma

Douglas B Johnson  1 , Igor Puzanov
Affiliations
Review

Treatment of NRAS-mutant melanoma

Douglas B Johnson et al. Curr Treat Options Oncol. 2015 Apr.

Abstract

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.

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Conflict of interest statement

Compliance with ethics guidelines: Conflict of interest: Douglas B. Johnson and Igor Puzanov declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
NRAS-driven cellular signalling and possible targeted therapeutic strategies.
See this image and copyright information in PMC

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