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Updated: Aug 9, 2025

Screening and Identification of Small Peptides Targeting Fibroblast Growth Factor Receptor2 using a Phage Display Peptide Library
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Fibroblast growth factor receptor type 4 as a potential therapeutic target in clear cell renal cell carcinoma

Takafumi Narisawa1, Sei Naito2, Hiromi Ito2

  • 1Department of Urology, Yamagata University Faculty of Medicine, 2-2-2 Iida-nishi, Yamagata, 990-9585, Japan. tnari_0623@yahoo.co.jp.

BMC Cancer
|February 21, 2023
PubMed
Abstract

Insights

Fibroblast growth factor receptor 4 (FGFR4) gene amplification drives clear cell renal cell carcinoma (ccRCC) growth. Inhibiting FGFR4 suppressed tumor progression, identifying it as a promising therapeutic target for ccRCC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Clear cell renal cell carcinoma (ccRCC) frequently exhibits fibroblast growth factor receptor 4 (FGFR4) gene copy number (CN) gains.
  • The functional role of FGFR4 CN amplification in ccRCC pathogenesis requires elucidation.

Purpose of the Study:

  • To investigate the functional significance of FGFR4 CN amplification in ccRCC.
  • To evaluate FGFR4 as a potential therapeutic target in ccRCC.

Main Methods:

  • Assessed correlation between FGFR4 CN (real-time PCR) and protein expression (western blotting, immunohistochemistry) in ccRCC cell lines and clinical specimens.
  • Utilized RNA interference and a selective FGFR4 inhibitor (BLU9931) to assess effects on ccRCC cell proliferation and survival (MTS assays, western blotting, flow cytometry).
  • Evaluated BLU9931 efficacy in a ccRCC xenograft mouse model.

Main Results:

  • FGFR4 CN amplification was observed in 60% of ccRCC specimens and correlated positively with protein expression.
  • FGFR4 amplification was present in ccRCC cell lines but not in a papillary RCC cell line (ACHN).
  • FGFR4 inhibition led to apoptosis and suppressed proliferation in ccRCC cells, with BLU9931 showing tumor suppression in vivo at tolerable doses.

Conclusions:

  • FGFR4 amplification promotes ccRCC cell proliferation and survival.
  • Targeting FGFR4 represents a potential therapeutic strategy for ccRCC patients with FGFR4 amplification.
Keywords:
BLU9931Clear cell renal cell carcinoma (ccRCC)FGFR4

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