In mouse melanoma brain metastases, a PI3K/mTOR inhibitor modified to optimally penetrate the blood–brain barrier achieved a response in all brain metastases.36 In BRAFV600-mutant melanoma brain metastases, a beneficial synergism of PI3K and MAPK inhibition in terms of growth inhibition and cell death induction was seen compared to the monotherapies.16,32,37–40 A promising treatment strategy for both BRAFV600-mutant and BRAF wild-type melanoma may be the combination of selective PI3K inhibitors with immune checkpoint inhibitors. This evidence concerns the gene PIK3CD and melanoma.