The Proteasome Inhibitor Bortezomib Is a Highly Effective Treatment Option for Gastroenteropancreatic Neuroendocrine Neoplasms and Sensitizes to DNA Damaging Therapy In Vitro

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Introduction: Gastroenteropancreatic neuroendocrine neoplasms are fairly rare tumors with very heterogeneous behavior and molecular characteristics. Their generally slow proliferation render them virtually resistant to many DNA damaging therapeutic approaches. Bortezomib has been shown to be effective in GEP-NENs in vitro but has been withdrawn from clinical assessment due to a small phase II study on bortezomib monotherapy in 2004.

Aim(s): The molecular and cell biological mechanisms of bortezomib activity was studied in vitro to assess the chemosensitizing effect in GEP-NENs.

Materials and methods: GEP-NEN cell lines of pancreatic and gastrointestinal offspring were treated with bortezomib, cisplatin or a combination of both treatments. The efficacy and molecular effects were studied by proliferation analyses, western blot, flow cytometry, HTCA and multiplexed gene expression analysis (Nanostring technologies).

Conference: 13th Annual ENETSConcerence (2016)

Presenting Author: Briest F

Authors: Briest F, Christen F, Worpenberg L, Welzel M, Freitag H,

Keywords: GEP-NEN, targeted therapy, DNA repair, chemotherapy,

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