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mTOR Pathway Inhibition Sensitizes Insulinoma Cells to Streptozotocin Induced Apoptosis


Introduction: Pancreatic neuroendocrine tumors (pNETs) are generally chemoresistants probably due to low proliferation rate and defects in apoptotic pathway. Targeted therapies are new encouraging options for pNETs however; clinical trials show limited objective response. Combination of chemotherapy and targeted therapy could be a new solution in therapeutic care. Streptozotocin (STZ) is the 1st line of therapy for unresectable pNETs.

Aim(s): Based on the literature, we hypothesized that mTOR pathway over-activation could lead to resistance to STZ.

Materials and methods: To evaluate this, we combined mTOR pathway inhibitors to STZ in in vitro and in vivo models. 4 mTOR pathway inhibitors (Everolimus, MK2206, BKM120 and BEZ235) were tested. Cell viability, proliferation and apoptosis were assessed in INS-1E cells (insulinoma cell line). Development of tumor nodules was analyzed in an intra-splenic xenograft model.

Conference: 12th Annual ENETSConcerence (2015)

Presenting Author: Vercherat C

Authors: Vercherat C, Walter T, Massoma-Peh P, Bollard J, Lacheretz-Bernigaud A,

Keywords: neuroendocrine, therapy, Streptozotocin, mTOR pathway, combination, pre-clinical study,

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