Related Experiment Video

Updated: Aug 7, 2025

A Mouse Model of Chronic Liver Fibrosis for the Study of Biliary Atresia
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A Mouse Model of Chronic Liver Fibrosis for the Study of Biliary Atresia

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Targeting Fibroblast Growth Factor Receptor Pathway: Precision Medicine for Biliary Cancer and Beyond

Pedro Luiz Serrano Uson Junior1,2, Mitesh J Borad1,3,4,5

  • 1Division of Hematology and Oncology, Department of Medicine, Mayo Clinic, Scottsdale, Arizona.

Seminars in Liver Disease
|March 7, 2023
PubMed

Insights

Fibroblast growth factor receptor 2 (FGFR2) inhibitors are effective treatments for advanced cholangiocarcinoma (CCA) with FGFR2 alterations. This review covers current FGFR inhibitors, clinical trials, and strategies to overcome resistance for improved patient outcomes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Advanced cholangiocarcinoma (CCA) treatment is evolving with targeted therapies.
  • Fibroblast growth factor receptor 2 (FGFR2) pathway activation drives CCA proliferation and progression.
  • FGFR2 alterations (fusions, rearrangements) are key targets in specific CCA patient populations.

Approach:

  • This review synthesizes current knowledge on FGFR inhibitors in advanced CCA.
  • It examines ongoing clinical trials and novel therapeutic molecules targeting the FGF-FGFR pathway.
  • Mechanisms of resistance to FGFR inhibitors and strategies to overcome them are discussed.

Key Points:

  • FGFR inhibitors show efficacy and can lead to durable responses in advanced CCA patients with FGFR2 fusions or rearrangements.
  • Next-generation sequencing and circulating tumor DNA analysis are crucial for identifying resistance mechanisms.
  • Understanding resistance is vital for developing more effective, selective drugs and combination therapies.

Conclusions:

  • Targeting the FGF-FGFR pathway is a validated strategy in advanced CCA.
  • Overcoming resistance mechanisms will be key to improving long-term patient outcomes.
  • Future research should focus on next-generation inhibitors and combination strategies informed by molecular profiling.

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