Erschienen in:
01.04.2015 | Skin Cancer (WH Sharfman, Section Editor)
Treatment of NRAS-Mutant Melanoma
verfasst von:
Douglas B. Johnson, M.D., Igor Puzanov, M.D.
Erschienen in:
Current Treatment Options in Oncology
|
Ausgabe 4/2015
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Opinion statement
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.