Taken together, these results indicated that the association of MEK1/2 and PI3K/mTOR inhibitors induces a more effective inhibition of p-ERK at both early and late time points compared to BRAF and PI3K/mTOR dual blockade, in PLX4720-resistant melanoma cells and even in cell lines with a cross-resistant phenotype. This evidence concerns the gene MAP2K1 and melanoma.