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Updated: Sep 23, 2025

Studying Chronic Exposure of Mice to Ultraviolet B Radiation
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Inhibition of Fibroblast Growth Factor Receptor Attenuates UVB-Induced Skin Carcinogenesis

Megha A Thakur1, Alok R Khandelwal2, Xin Gu3

  • 1Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, Texas, USA.

The Journal of Investigative Dermatology
|May 13, 2022
PubMed

Insights

Inhibiting fibroblast growth factor receptor (FGFR) signaling in mouse skin suppressed UVB-induced skin cancer development. This suggests FGFR inhibition may be a new strategy for preventing and treating cutaneous squamous cell carcinoma.

Area of Science:

  • Oncology
  • Dermatology
  • Molecular Biology

Background:

  • Aberrant fibroblast growth factor receptor (FGFR) signaling is implicated in various cancers.
  • The specific role of FGFR signaling in UVB-induced cutaneous squamous cell carcinoma (cSCC) is not well understood.

Purpose of the Study:

  • To investigate the effect of UVB radiation on FGFR activation and downstream signaling in mouse skin epidermis.
  • To determine the impact of FGFR inhibition on UVB-induced signaling and skin carcinogenesis.

Main Methods:

  • Mice were exposed to UVB radiation, and FGFR activation and downstream pathways (mTOR, STAT, MAPK) were analyzed.
  • A pan-FGFR inhibitor (AZD4547) was applied topically before UVB exposure.
  • Effects on epidermal hyperplasia, immune cell infiltration, inflammatory gene expression, cSCC incidence, and survival were assessed.

Main Results:

  • UVB exposure increased FGFR phosphorylation and downstream signaling in mouse epidermis.
  • AZD4547 treatment inhibited UVB-induced FGFR phosphorylation, downstream signaling, epidermal hyperplasia, and inflammatory gene expression.
  • FGFR inhibition reduced mast cell and macrophage infiltration into the dermis.
  • AZD4547 pretreatment significantly decreased cSCC incidence and increased survival rates in mice.

Conclusions:

  • FGFR signaling is activated by UVB radiation and contributes to skin carcinogenesis.
  • Inhibition of FGFR signaling with AZD4547 effectively suppresses UVB-induced skin cancer development.
  • Targeting FGFR in the epidermis presents a potential therapeutic strategy for preventing and treating cSCC.

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