title: Targeting Fibroblast Growth Factor Receptor (FGFR) with BGJ398 in a Gastric Cancer Model.
abstract: OBJECTIVE
  To assess the efficacy of targeting fibroblast growth factor receptor (FGFR) with the pan-FGFR inhibitor BGJ398 in a gastric cancer (GC) model.
  
  
  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.
  
  
  CONCLUSIONS
  Efficacy of FGFR inhibition is dependent on FGFR1 and FGFR2IIIc expression in GC models.
authors.affiliation: Department of Surgery, University Hospital Regensburg, University of Regensburg, Regensburg, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Schmidt
authors.affiliation: Department of Surgery, University Hospital Regensburg, University of Regensburg, Regensburg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Moser
authors.affiliation: Department of Internal Medicine I, University Hospital Regensburg, University of Regensburg, Regensburg, Germany.
authors.forename: Claus
authors.initials: C
authors.lastname: Hellerbrand
authors.affiliation: Department of General and Transplant Surgery and Comprehensive Cancer Center, University of Tuebingen, Tuebingen, Germany.
authors.forename: Derek
authors.initials: D
authors.lastname: Zieker
authors.affiliation: Department of Surgery, University Hospital Regensburg, University of Regensburg, Regensburg, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Wagner
authors.affiliation: Department of Surgery, University Hospital Regensburg, University of Regensburg, Regensburg, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Redekopf
authors.affiliation: Department of Surgery, University Hospital Regensburg, University of Regensburg, Regensburg, Germany.
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Schlitt
authors.affiliation: Department of Surgery, University Hospital Regensburg, University of Regensburg, Regensburg, Germany.
authors.forename: Edward K
authors.initials: EK
authors.lastname: Geissler
authors.affiliation: Department of Surgery, University Hospital Regensburg, University of Regensburg, Regensburg, Germany sven.lang@ukr.de.
authors.forename: Sven A
authors.initials: SA
authors.lastname: Lang
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006801:Humans; D010671:Phenylurea Compounds / Q000378:metabolism*; D011743:Pyrimidines / Q000378:metabolism*; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism*
chemical_list: D010671:Phenylurea Compounds; D011743:Pyrimidines; C568950:infigratinib; D051496:Receptor, Fibroblast Growth Factor, Type 1
keywords: FGFR; angiogenesis; gastric cancer