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Fibroblast growth factor receptor (FGFR) gene: pathogenesis and treatment implications in urothelial carcinoma of the bladder
  1. Khaleel I Al-Obaidy1,
  2. Liang Cheng1,2
  1. 1Department of Pathology, Indiana University School of Medicine, Indianapolis, Indiana, USA
  2. 2Department of Urology, Indiana University School of Medicine, Indianapolis, Indiana, USA
  1. Correspondence to Dr Liang Cheng, Pathology & Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA; liang_cheng{at}


Dysregulation of fibroblast growth factor receptors (FGFRs) has been implicated in several human malignancies, including urothelial carcinoma. In urothelial carcinoma, the oncogenic role of mutated FGFR is mediated by the RAS-mitogen-activated protein kinase pathway, resembling the effects observed with activated HRAS. Activating somatic mutations of FGFR3 are clustered in three hotspots in exons 7, 10 and 15, and are almost always missense mutations leading to amino acid substitution in the external, transmembrane or intracellular regions of the receptor. A fusion of FGFR3 to transforming acid coiled-coil containing protein 3, FGFR3 amplification and alternative splicing leading to aberrant FGFR3 activation are less common molecular alterations. In April 2020, the Food and Drug Administration (FDA) approved the first targeted FGFR therapy, erdafitinib, in patients with locally advanced or metastatic bladder cancer who have progressed on platinum-based chemotherapy. Herein, we reviewed the normal structure and function of FGFR. We also explored its role in the development of urothelial carcinoma and major developments in the FGFR-targeted therapy.

  • diagnosis
  • urologic neoplasms
  • urologic diseases
  • pathology
  • molecular
  • male urogenital diseases

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  • Handling editor Des Richardson.

  • Contributors All authors contributed to the conception of the work, revised it critically and approved the final version.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.