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Semin Liver Dis 2023; 43(02): 218-225
DOI: 10.1055/a-2049-3149
Review Article

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

Pedro Luiz Serrano Uson Junior
1   Division of Hematology and Oncology, Department of Medicine, Mayo Clinic, Scottsdale, Arizona
2   Center for Personalized Medicine, Hospital Israelita Albert Einstein, São Paulo, Brazil
,
Mitesh J. Borad
1   Division of Hematology and Oncology, Department of Medicine, Mayo Clinic, Scottsdale, Arizona
3   Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota
4   Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota
5   Mayo Clinic Cancer Center, Mayo Clinic, Phoenix, Arizona
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Abstract

Fibroblast growth factor receptor 2 (FGFR2) inhibitors are now being included in the treatment guidelines of multiple countries for patients with advanced cholangiocarcinoma (CCA). Activation of the FGF–FGFR pathway is related to proliferation and tumor progression. Targeting the FGF–FGFR pathway is effective and can yield durable responses in patients with CCA harboring FGFR2 fusions or rearrangements. In this review article, we address molecules and clinical trials evaluating FGFR inhibitors in advanced CCA. We will further discuss identified mechanisms of resistance and the strategies to overcome it. The incorporation of next-generation sequencing in advanced CCA and circulating tumor DNA on disease progression will unveil mechanisms of resistance and improve the development of future clinical trials and more selective drugs and combinations.

Keywords

cholangiocarcinoma - FGFR2 - biliary cancers - pemigatinib - infigratinib - futibatinib


Publication History

Accepted Manuscript online:
07 March 2023

Article published online:
29 March 2023

© 2023. Thieme. All rights reserved.

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