Since signaling through the PI3K/AKT/mTOR pathway has been implicated in intrinsic resistance to BRAF or MEK inhibitor therapy, we investigated if individual or pan isoform inhibitors of PI3K and/or mTOR could enhance the antitumor activity of BRAF/MEK inhibitors in BRAF-mutant melanoma cell lines that are sensitive to BRAF/MEK inhibition. This evidence concerns the gene PIK3CA and melanoma.