Efficient Suppression of NRAS-Driven Melanoma by Co-Inhibition of ERK1/2 and ERK5 MAPK Pathways.

Cutaneous melanoma is a highly malignant tumor typically driven by somatic mutation in the oncogenes BRAF or NRAS, leading to uncontrolled activation of the MEK/ERK MAPK pathway. Despite the availability of immunotherapy, MAPK pathway‒targeting regimens are still a valuable treatment option for BRAF-mutant melanoma. Unfortunately, patients with NRAS mutation do not benefit from such therapies owing to the lack of targetable BRAF mutations and a high degree of intrinsic and acquired resistance toward MEK inhibition.