BEZ235 + BKM120

**BEZ235 + BKM120** is a combination of two small molecule kinase inhibitors developed by Novartis for investigation in advanced cancers. BEZ235 (dactolisib) is a dual **PI3K/mTOR inhibitor** targeting class I PI3K isoforms (p110α/γ/δ/β) and mTOR (p70S6K) with IC50 values around 4 nM, inducing G1 cell cycle arrest in tumor cells. BKM120 (buparlisib) is an oral **pan-PI3K inhibitor** acting on all four class I PI3K isoforms (α, β, γ, δ), demonstrating antiproliferative and pro-apoptotic effects in cancer models. The combination was tested orally in phase Ib trials, often with endocrine therapy or abiraterone acetate, primarily in hormone receptor-positive breast cancer and castration-resistant prostate cancer, but development was halted due to limited efficacy, variable pharmacokinetics, and toxicity issues like hyperglycemia, mood alterations, liver toxicity, and pneumonitis.[1][2][3][4][5][6][7]