Enhanced FGFR signalling predisposes pancreatic cancer to the effect of a potent FGFR inhibitor in preclinical models.

ABSTRACT:

Background

Fibroblast growth factor receptor (FGFR) signalling has been implicated in pancreas carcinogenesis. We investigated the effect of FGFR inhibition in pancreatic cancer in complementary cancer models derived from cell lines and patient-derived primary tumour explants.

Methods

The effects of FGFR signalling inhibition in pancreatic cancer were evaluated using anti-FRS2 shRNA and dovitinib. Pancreatic cancers with varying sensitivity to dovitinib were evaluated to determine potential predictive biomarkers of efficacy. Primary pancreatic explants with opposite extreme of biomarker expression were selected from 13 tumours for in vivo dovitinib treatment.

Results

Treatment with anti-FRS2 shRNA induced significant in vitro cell kill in pancreatic cancer cells. Dovi

SUBMITTER: Zhang H 

PROVIDER: S-EPMC3899776 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature