Selective Inhibition of PI3Kalpha (BYL719) - Promising Therapeutic Option for Neuroendocrine Tumors?

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Introduction: Neuroendocrine tumors are heterogeneous, often functional malignancies and their therapeutic options are limited. As the PI3 kinase signaling is ­in GEP-NENs, selective PI3Kalpha inhibitors may be more potent than panPI3K inhibitors.

Aim(s): Therefore, we assessed the effects of BYL719 in different NEN cell lines (pancreatic and lung NET) compared to the established mTORC1 inhibitor everolimus

Materials and methods: We treated the cell lines BON, QGP-1, NCI-H727 with increasing concentrations of the inhibitor BYL-719, compared to everolimus and DMSO. We performed WST-1 assay in order to determine efficacy and growth inhibition. The induction of apoptosis was shown by caspase 3/7 activation and cell cycle was analyzed by FACS. We determined changes in the signaling network by phospho-specific western blot analysis.

Conference: 13th Annual ENETSConcerence (2016)

Presenting Author: Grabowski P

Authors: Nölting S, Rentsch J, Freitag H, Briest F, Schrader J,

Keywords: PI3Kalpha, BYL719, neuroendocrine tumor cell lines,