Investigation of FGR2 Mutation in Gallbladder Cancers with Pemigatinib Application

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Boz A. B.

II. Uluslararası Mezopotamya Kongresi, Şanlıurfa, Türkiye, 31 Temmuz - 02 Ağustos 2026, ss.1-2, (Özet Bildiri)

  • Yayın Türü: Bildiri / Özet Bildiri
  • Basıldığı Şehir: Şanlıurfa
  • Basıldığı Ülke: Türkiye
  • Sayfa Sayıları: ss.1-2
  • Recep Tayyip Erdoğan Üniversitesi Adresli: Evet

Özet

Title: Integrin Inhibition Prevents Pemigatinib-Induced EMT and Stemness Activation in FGFR2-Mutant Gallbladder Cancer Cells

Authors: Asiye Busra Boz

Affiliations: Department of Medical Biology, Faculty of Medicine, Recep Tayyip Erdogan University, Rize 53100, Turkey

Background and Aims: Biliary tract cancers (BTCs), including intrahepatic and extrahepatic cholangiocarcinomas as well as gallbladder carcinomas, are rare malignancies, accounting for approximately 3% of all gastrointestinal cancers worldwide. Despite their low incidence, BTCs are associated with poor prognosis due to late diagnosis and limited therapeutic options. Activating alterations in FGFR2, including mutations and fusions, are frequently observed in BTCs, particularly in intrahepatic subtypes, and represent actionable molecular targets for precision therapy. Although Pemigatinib, a selective FGFR inhibitor, has demonstrated clinical efficacy in patients with FGFR2 aberrations, the temporal effects of FGFR inhibition on epithelial-mesenchymal transition (EMT) and cancer stemness remain poorly characterized. The aim of this study was to investigate both short- and long-term effects of Pemigatinib alone and in combination with the integrin inhibitor Cilengitide on EMT and stemness markers in FGFR2-mutant (SNU1079, ICC13-7) and FGFR2 wild-type (HuCCT1) gallbladder cancer cell lines.

Methods: FGFR2-mutant SNU1079 and ICC13-7, and FGFR2 wild-type HuCCT1 cells were treated with Pemigatinib at IC50 concentrations determined by MTT assays. For combination experiments, cells were co-treated with Pemigatinib and Cilengitide according to Chou-Talalay method. Cells were harvested at 0, 4, 8, 12, 16, 20, and 40 days post-treatment. Real-time PCR was used to assess the expression of stemness-associated transcription factors (Sox2, Oct4, Nanog, Klf4, ALDH1) and EMT-associated regulators (Slug, Snail, Twist2, Zeb1).

Results: In FGFR2-mutant SNU1079 and ICC13-7 cells treated with Pemigatinib alone, stemness and EMT markers showed a progressive and consistent increase beginning at day 16, while in FGFR2 wild-type HuCCT1 cells, significant upregulation was only observed at day 40. Remarkably, in all cell lines co-treated with Pemigatinib and Cilengitide, no increase in stemness or EMT markers was observed at any time point.

Conclusion: FGFR2-mutant gallbladder cancer cells exhibit earlier and sustained activation of EMT and stemness pathways in response to Pemigatinib treatment, whereas FGFR2 wild-type cells show delayed responses. Importantly, combined inhibition of FGFR and integrins with Cilengitide completely blocked the upregulation of EMT and stemness markers observed with Pemigatinib monotherapy. These findings suggest that integrin-mediated signaling contributes to adaptive responses and potential resistance mechanisms in FGFR2-targeted therapy. Combination strategies targeting both FGFR2 and integrin pathways may therefore enhance therapeutic efficacy and prevent or delay the development of resistance in biliary tract cancers.