MAP2K1 and melanoma: Although BRAF-mutant melanoma is currently treatable with BRAF and MEK inhibitors in combination therapies, acquired resistance in ~75% of melanomas can occur by reactivation of MAPK signaling after BRAF copy number gains and alternative splicing, or MEK1/2 and NRAS gain-of-function mutations; an additional 20% of BRAF inhibitor-resistant melanomas acquire mutations or upregulate compensatory PI3K/AKT survival pathways [9].