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Fibroblast growth factor receptor fusions in cancer: opportunities and challenges

Lingfeng Chen1,2, Yanmei Zhang3, Lina Yin3

  • 1Clinical Pharmacy Center, Department of Pharmacy, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, 310014, Zhejiang, China. lfchen@hmc.edu.cn.

Journal of Experimental & Clinical Cancer Research : CR
|November 4, 2021
PubMed

Insights

Fibroblast growth factor receptor (FGFR) fusions drive cancer by causing abnormal signaling. FGFR inhibitors like erdafitinib and pemigatinib show promise in treating specific cancers, with new drugs in development.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Fibroblast growth factors (FGFs) and their receptors (FGFRs) are crucial for biological processes.
  • Aberrant signaling from FGFR fusions, caused by chromosomal translocations, drives human cancer development and progression.

Purpose of the Study:

  • To review the FGF/FGFRs system and the oncogenic role of FGFR fusions.
  • To summarize FGFR inhibitors targeting fusions currently in clinical development.
  • To highlight existing challenges in targeting FGFR fusions.

Main Methods:

  • Literature review of FGF/FGFRs signaling pathways.
  • Analysis of clinical trial data for FGFR inhibitors.
  • Synthesis of current research on oncogenic FGFR fusions.

Main Results:

  • FGFR fusions are validated oncogenic drivers and therapeutic targets.
  • Approved FGFR inhibitors (erdafitinib, pemigatinib) treat urothelial cancer and cholangiocarcinoma.
  • Third-generation inhibitors like futibatinib are in clinical trials for FGFR gene rearrangements.

Conclusions:

  • Targeting FGFR fusions represents a significant advancement in precision oncology.
  • Ongoing research and clinical trials are expanding therapeutic options for cancers with FGFR alterations.
  • Overcoming challenges in FGFR fusion targeting is critical for improving patient outcomes.
Keywords:
CancerChromosomal translocationFibroblast growth factor receptorsFusion proteinsInhibitors

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