Saskia M. Brachmann

TL;DR: The preclinical data show that NVP-BEZ235 is a potent dual PI3K/mTOR modulator with favorable pharmaceutical properties, and the compound was well tolerated, displayed disease stasis when administered orally, and enhanced the efficacy of other anticancer agents when used in in vivo combination studies.

TL;DR: A large-scale RNAi screen is conducted in which viability effects of mRNA knockdown were assessed for 7,837 genes using an average of 20 shRNAs per gene in 398 cancer cell lines, outlining the classes of cancer dependency genes and their relationships to genetic, expression, and lineage features.

TL;DR: The biologic characterization of the 2-morpholino pyrimidine derivative pan-PI3K inhibitor NVP-BKM120 shows dose-dependent in vivo pharmacodynamic activity as measured by significant inhibition of p-Akt and tumor growth inhibition in mechanistic xenograft models and behaves synergistically when combined with either targeted agentssuch as MEK or HER2 inhibitors or with cytotoxic agents such as docetaxel or temozolomide.

TL;DR: The biologic properties of the 2-aminothiazole derivative NVP-BYL719, a selective inhibitor of PI3Kα and its most common oncogenic mutant forms, are reported and it is found that PIK3CA mutation was the foremost positive predictor of sensitivity while revealing additional positive and negative associations such as Pik3CA amplification and PTEN mutation, respectively.

TL;DR: An in depth analysis of death markers revealed that the cell death observed upon NVP-BEZ235 treatment could be recapitulated with other PI3K inhibitors and that this event is linked to active PARP cleavage indicative of an apoptotic process.