Role of FOXM1 in Aggressive Pancreatic / Pulmonary Neuroendocrine Carcinomas and Anti-Tumor Effect of the FOXM1 Inhibitor Thiostrepton

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Introduction: DNA-targeting agents are the main treatment of aggressive pulmonary and pancreatic neuroendocrine carcinomas (NEC). FOXM1 is a transcription factor controlling cell proliferation and DNA repair pathways, playing therefore an important role in tumor progression and chemoresistance.

Aim(s): Assess the prognostic/predictive value of FOXM1 expression in pancreatic and pulmonary NECs and evaluate in vitro the potential antitumoral effect of Thiostrepton (TS), a FOXM1 inhibitor.

Materials and methods: FOXM1 expression (immunohistochemistry) was determined in a comprehensive retrospective cohort of pancreatic and pulmonary NECs treated by etoposide/carboplatin (EC). TS antiproliferative effect alone or with EC was assessed in vitro in BON-1/QGP-1 (pancreas) and H-227 (lung) cell lines and its mechanisms of action studied by RNAseq and dynamic DNA repair tests.

Conference: 17th Annual ENETSConcerence (2020)

Presenting Author: Cros J

Authors: De Rycke O, Raffenne J, Lacombe C, Hentic O, Gounant V,

Keywords: neuroendocrine carcinoma, FOXM1, DNA repair, anti-tumor drug,

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