Mitochondrial or Aerobic Glycolysis Oriented Metabolism May Define Pancreatic Neuroendocrine Tumors (PanNET) Resistance to mTOR-Targeting Therapies

#2287

Introduction: The mTOR inhibitor Everolimus is approved for the treatment of PanNET and no predictive biomarker is available. mTOR is a central node controlling mitochondrial and aerobic glycolytic metabolisms.

Aim(s): Define predictive biomarkers for Everolimus in PanNET

Materials and methods: 300uM slices of 15 fresh PanNET were cultured ex vivo for 48h with no drug or everolimus. Resistance was defined by Caspase 3 levels assessed by immunohistochemistry at 48h. Proteins and RNA from the frozen corresponding tumors were extracted. Transcriptomic profiles were determined and key proteins involved in metabolic pathways quantified by reverse phase protein array (RPPA) and immunohistochemistry (IHC). A validation cohort of 17 patients with a PNET treated by Everolimus was used.

Conference: 15th Annual ENETSConcerence (2018)

Presenting Author:

Authors: Cros J, Bucau M, Raffenne J, Soukeur M, Dumont F,

Keywords: mTOR, everolimus, pancreatic NET, metabolism,