MAP2K1 and metastatic melanoma: In unresectable or metastatic melanoma with a BRAF V600-activating mutation, combination regimens targeting BRAF and MEK1/MEK2 have shown long-term clinical benefit and are recommended therapy options.1–9 Approximately 50% of metastatic melanomas have point mutations in BRAF, with the most common, V600E, present in about 85% of BRAF-mutated melanomas.10BRAF V600 mutations activate the mitogen-activated protein kinase (MAPK) pathway downstream of RAS, leading to tumor proliferation.