BRAF and MEK inhibitor combinations induce potent molecular and immunological effects in NRAS-mutant melanoma cells: Insights into mode of action and resistance mechanisms.

About 25% of melanoma harbor activating NRAS mutations, which are associated with aggressive disease therefore requiring a rapid antitumor intervention. However, no efficient targeted therapy options are currently available for patients with NRAS-mutant melanoma. MEK inhibitors (MEKi) appear to display a moderate antitumor activity and also immunological effects in NRAS-mutant melanoma, providing an ideal backbone for combination treatments.

Head-to-Head Comparison of BRAF/MEK Inhibitor Combinations Proposes Superiority of Encorafenib Plus Trametinib in Melanoma.

BRAFV600 mutations in melanoma are targeted with mutation-specific BRAF inhibitors in combination with MEK inhibitors, which have significantly increased overall survival, but eventually lead to resistance in most cases. Additionally, targeted therapy for patients with NRASmutant melanoma is difficult. Our own studies showed that BRAF inhibitors amplify the effects of MEK inhibitors in NRASmutant melanoma.