BKM120

BKM120 (NVP-BKM120) is a novel phosphatidylinositol 3-kinase (PI3K) inhibitor and is currently being investigated in phase I clinical trials in solid tumors. Unlike other inhibitors, it does not inhibit the related kinases-mTOR and Vps34. BKM120 (NVP-BKM120) has shown significant cell growth inhibition and induction of apoptosis in a variety of tumor cell lines as well as in animal models, it decreases the cellular levels of p-Akt in mechanistic models and relevant tumor cell lines, as well as downstream effectors in a concentration-dependent and pathway-specific manner. Tested in a panel of 353 cell lines, BKM120 (NVP-BKM120) exhibited preferential inhibition of tumor cells bearing PIK3CA mutations, in contrast to either KRAS or PTEN mutant models. BKM120 treatment significantly inhibits tumor growth in vivo and prolongs the survival of myeloma-bearing mice. In addition, it shows synergistic cytotoxicity with dexamethasone in dexamethasone-sensitive MM cells. BKM120 (NVP-BKM120) behaves synergistically when combined with either targeted agents such as MEK or HER2 inhibitors or with cytotoxic agents such as docetaxel or temozolomide.