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PAK4-NAMPT Dual Inhibition as a Novel Strategy for Therapy Resistant Pancreatic Neuroendocrine Tumors


Introduction: Pancreatic neuroendocrine tumors (PNET) remain an unmet clinical need. In this study, we show that targeting both nicotinamide phosphoribosyltransferase (NAMPT) and p21-activated kinase 4 (PAK4) could become a synthetic lethal strategy for PNET.

Aim(s): The goal of this study is to delineate the mechanism of drug resistance and design a broad form of clinically viable therapeutic strategy for the difficult to treat PNETs.

Materials and methods: PNET cell lines were exposed to KPT-9274 single agent and in combination with everolimus. Cell growth inhibition was evaluated using MTT, clonogenic and cell Titer-Glo assays. Apoptosis and cell death were analyzed using Annexin V FITC and 7-Aminoactinomycin D (7AAD) assay. Protein expression and mRNA expression changes were evaluated using Western blot and RT-PCR. The antitumor activity of KPT-9274 was also evaluated in PNETs subcutaneous xenograft.

Conference: 17th Annual ENETSConcerence (2020)

Presenting Author: Mpilla G

Authors: Mpilla G, Aboukameel A, Muqbil I, Kim S, Philip P,

Keywords: pak4, nampt, mtor, pancreatic neuroendocrine tumors, kpt-9274,

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