Blockade Of The Pi3k-Alpha Isoform To Inhibit Myeloma Cells.

e19573 Background: Both, the phosphoinositide-3 kinase (PI3K)/AKT pathway as well as its downstream target, the mToR (mammalian target of rapamycin) kinase, are essential for the growth and survival of malignant plasma cells. PI3K exists in four isotypes (α - δ), which role is not defined in multiple myeloma (MM). Therefore, we evaluated systematically the anti-myeloma activity of BYL719, an inhibitor newly developed by Novartis Pharma and highly selective for the PI3Kα isoform. The activity of BYL719 was compared with other inhibitors of the PI3K/AKT/mToR signaling network. Methods: An MTS based growth assay with six human malignant plasma cell lines and two non-myeloma cell lines was used to measure growth inhibition of BYL719 in comparison to other inhibitors, namely the pan-PI3K inhibitors Ly294002 and BKM120, the dual PI3K/mToR inhibitor BEZ235, and the allosteric mToR inhibitors rapamycin and everolimus. Western blot analysis was used to confirm inhibitor activity and specificity. In addition, combi...