A dual pathway inhibition strategy using BKM120 combined with vemurafenib is poorly tolerated in BRAF V600 E/K mutant advanced melanoma.

Single or dual agent inhibition of the MAPK pathway can induce objective responses in up to 70% of BRAF mutant melanoma patients, but these responses are transient in most patients (e. g. Long et al., 2015). Aberrant signaling in the PI3K pathway has been implicated in both melanoma oncogenesis and in BRAF inhibitor resistance (e. g. Dankort et al., 2009; Goel et al., 2006). PTEN loss, which leads to increased PI3K activity, is common in patients treated with the BRAF inhibitor vemurafenib (McArthur et al., 2011) and decreased PTEN expression has been identified as a predictor of decreased PFS in patients treated with the drug (Nathanson et al., 2013). This article is protected by copyright. All rights reserved.