In line with the concept that combined RAF/MEK/ERK and PI3K/AKT/mTOR inhibition is selectively synergistic in PTEN-loss contexts, Daphu et al. have demonstrated that combined therapy with the BRAF inhibitor Vemurafenib and the mTOR inhibitor Temsirolimus is highly synergistic, as compared to single-drug treatment, in cell lines derived from human melanoma brain metastases harboring both a BRAF mutation and PTEN-loss25. This evidence concerns the gene BRAF and melanoma.