The Role of MAPK-Signalling in Pancreatic Neuroendocrine Cancer

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Introduction: Upon diagnosis, 65% of pNET patients suffer from metastatic or locally unresectable disease. The receptor tyrosine kinase inhibitor sunitinib and the mTOR inhibitor everolimus have set precedence for successful targeted therapies in pNET disease. However, response prediction and treatment alternatives still do not meet medical needs. Recent studies revealed mutations in RAS oncogenes in a fraction of tumours, emphasising a potential role of the MAPK pathway as therapeutic target.

Aim(s): To study the consequences of pharmacologic inactivation of MEK or ERK kinases in pNET cells.

Materials and methods: BON-1 and QGP-1 cell lines are treated with either MEK or ERK inhibitors. Live cell analysis is performed to determine efficacy and growth inhibition. Induction of apoptosis is shown by cleaved caspase-3 and cell cycle regulation is analysed by flow cytometry. Changes in the MAPK and mTOR signalling network are determined by western blots and multiplex immunoassays.

Conference: 14th Annual ENETSConcerence (2017)

Presenting Author:

Authors: Hoffmann J, Corbett L, Detjen K, Thedieck K, Sers C,

Keywords: pancreatic neuroendocrine tumors, MAPK pathway,