JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
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Targeting Fibroblast Growth Factor Receptor (FGFR) with BGJ398 in a Gastric Cancer Model.

Anticancer Research 2015 December
AIM: To assess the efficacy of targeting fibroblast growth factor receptor (FGFR) with the pan-FGFR inhibitor BGJ398 in a gastric cancer (GC) model.

MATERIALS AND METHODS: Expression of FGFRs was determined in GC cell lines (KKLS, MKN-45, TMK-1). Impact of the FGFR inhibitor BGJ398 on growth, motility, signaling, expression of transcription factors and secretion of vascular endothelial growth factor-A (VEGFA) was determined in vitro. Results were validated in subcutaneous tumor models.

RESULTS: In vitro, FGFR inhibition was most effective in KKLS cells (high FGFR1, FGFR2IIIc, no FGFR2IIIb expression) with inhibition of growth, motility, signaling, c-MYC expression and VEGFA secretion. BGJ398 showed some activity in MKN-45 cells (intermediate FGFR1, high FGFR2IIIb, low FGFR2IIIc expression), while TMK-1 cells (low FGFR1, no FGFR2IIIb and FGFR2IIIc expression) did not respond. Results were confirmed in vivo with strongest efficacy on growth in KKLS tumors and only minor impairment of TMK-1 lesions.

CONCLUSION: Efficacy of FGFR inhibition is dependent on FGFR1 and FGFR2IIIc expression in GC models.

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