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Updated: May 30, 2025

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FGF-based drug discovery: advances and challenges

Gaozhi Chen1, Lingfeng Chen2, Xiaokun Li3

  • 1School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.

Nature Reviews. Drug Discovery
|January 28, 2025
PubMed

Insights

Fibroblast growth factors (FGFs) are key regulators of human development and metabolism. Recent insights into paracrine FGF signaling mechanisms reveal potential for treating metabolic diseases.

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Drug Development

Background:

  • The fibroblast growth factor (FGF) family includes 15 paracrine and 3 endocrine polypeptides crucial for development, metabolism, and tissue homeostasis.
  • While endocrine FGFs (e.g., FGF19, FGF21) show therapeutic promise for liver and metabolic diseases, paracrine FGFs have faced development challenges.
  • Paracrine FGFs, despite past failures in areas like wound healing, are regaining interest due to their newly recognized hormone-like metabolic activities.

Purpose of the Study:

  • To explore the therapeutic potential of paracrine fibroblast growth factors (FGFs) for metabolic diseases.
  • To highlight recent advancements in understanding FGF signaling specificity and its implications for drug development.

Main Methods:

  • Review of existing literature on fibroblast growth factor (FGF) family functions.
  • Analysis of recent structural and mechanistic studies on FGF cell surface signaling.
  • Evaluation of the 'threshold model' for FGF signaling specificity.

Main Results:

  • Paracrine FGFs exhibit previously unrecognized FGF hormone-like metabolic activities.
  • Structural elucidation of FGF signaling machinery provides new insights.
  • A novel threshold model explains FGF signaling specificity.

Conclusions:

  • The understanding of paracrine FGFs has shifted, revealing their potential beyond traditional applications.
  • Recent breakthroughs in FGF signaling mechanisms pave the way for developing novel therapies.
  • Paracrine FGFs represent a promising, yet previously overlooked, therapeutic avenue for metabolic diseases.

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