Open AccessCurrent Perspectives and Novel Strategies of NRAS-Mutant Melanoma
Author(s) -
Alejandro García-Alvarez,
Carolina Ortiz,
Eva MuñozCouselo
Publication year - 2021
Publication title -
oncotargets and therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.054
H-Index - 60
ISSN - 1178-6930
DOI - 10.2147/ott.s278095
Subject(s) - neuroblastoma ras viral oncogene homolog , melanoma , medicine , pi3k/akt/mtor pathway , immunotherapy , oncology , cancer research , mutant , clinical trial , targeted therapy , cancer , signal transduction , biology , genetics , colorectal cancer , gene , kras
Melanoma is the deadliest cutaneous cancer. Activating mutations in NRAS are found in 20% of melanomas. NRAS -mutant melanoma is more aggressive and, therefore, has poorer outcomes, compared to non- NRAS -mutant melanoma. Despite promising preclinical data, to date immune checkpoint inhibitors remain the standard of care for locally advanced unresectable or metastatic NRAS melanoma. Data for efficacy of immunotherapy for NRAS melanoma mainly come from retrospective cohorts with divergent conclusions. MEK inhibitors have been the most developed targeted therapy approach. Although associated with an increase in progression-free survival, MEK inhibitors do not provide any benefit in terms of overall survival. Combination strategies with PI3K-AKT-mTOR pathway and CDK4/6 inhibitors seem to increase MEK inhibitors' benefit. Nevertheless, results from clinical trials are still prelaminar. A greater comprehension of the biology and intracellular interactions of NRAS -mutant melanoma will outline novel impactful strategies which could improve prognosis of these subgroup of patients.