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FGFR Inhibitors: Clinical Activity and Development in the Treatment of Cholangiocarcinoma

  • Evolving Therapies (RM Bukowski, Section Editor)
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Abstract

Purpose of Review

Cholangiocarcinoma is an aggressive cancer with a poor prognosis and limited treatment. Gene sequencing studies have identified genetic alterations in fibroblast growth factor receptor (FGFR) in a significant proportion of cholangiocarcinoma (CCA) patients. This review will discuss the FGFR signaling pathway’s role in CCA and highlight the development of therapeutic strategies targeting this pathway.

Recent Findings

The development of highly potent and selective FGFR inhibitors has led to the approval of pemigatinib for FGFR2 fusion or rearranged CCA. Other selective FGFR inhibitors are currently under clinical investigation and show promising activity. Despite encouraging results, the emergence of resistance is inevitable. Studies using circulating tumor DNA and on-treatment tissue biopsies have elucidated underlying mechanisms of intrinsic and acquired resistance. There is a critical need to not only develop more effective compounds, but also innovative sequencing strategies and combinations to overcome resistance to selective FGFR inhibition. Therapeutic development of precision medicine for FGFR-altered CCA is a dynamic process of involving a comprehensive understanding of tumor biology, rational clinical trial design, and therapeutic optimization.

Summary

Alterations in FGFR represent a valid therapeutic target in CCA and selective FGFR inhibitors are treatment options for this patient population.

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Authors and Affiliations

  1. Division of Medical Oncology, University of Washington, Seattle, WA, USA

    Gentry King

  2. Seattle Cancer Care Alliance, 825 Eastlake Avenue East, LG-465, Seattle, WA, 98109, USA

    Gentry King

  3. Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    Gentry King

  4. Department of Gastrointestinal (GI) Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 0426, Houston, TX, 77030-4009, USA

    Milind Javle

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Correspondence to Milind Javle.

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Gentry King declares that he has no conflict of interest. Milind Javle has received research funding from QED Therapeutics, Taiho Pharmceutical Group, Basilea Pharmaceutical AG, EMD Serono, Meclun, AstraZeneca, and Merck; and has received compensation for service as a consultant from QED Therapeutics, Taiho, EMD Serono, AstraZeneca, and Merck.

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King, G., Javle, M. FGFR Inhibitors: Clinical Activity and Development in the Treatment of Cholangiocarcinoma. Curr Oncol Rep 23, 108 (2021). https://doi.org/10.1007/s11912-021-01100-3

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