Therapeutics Targeting FGF Signaling Network in Human Diseases

Trends Pharmacol Sci. 2016 Dec;37(12):1081-1096. doi: 10.1016/j.tips.2016.10.003. Epub 2016 Oct 27.

Abstract

Fibroblast growth factor (FGF) signaling through its receptors, FGFR1, FGFR2, FGFR3, or FGFR4, regulates cell fate, angiogenesis, immunity, and metabolism. Dysregulated FGF signaling causes human diseases, such as breast cancer, chondrodysplasia, gastric cancer, lung cancer, and X-linked hypophosphatemic rickets. Recombinant FGFs are pro-FGF signaling therapeutics for tissue and/or wound repair, whereas FGF analogs and gene therapy are under development for the treatment of cardiovascular disease, diabetes, and osteoarthritis. FGF traps, anti-FGF/FGFR monoclonal antibodies (mAbs), and small-molecule FGFR inhibitors are anti-FGF signaling therapeutics under development for the treatment of cancer, chondrodysplasia, and rickets. Here, I discuss the benefit-risk and cost-effectiveness issues of precision medicine targeting FGFRs, ALK, EGFR, and FLT3. FGFR-targeted therapy should be optimized for cancer treatment, focusing on genomic tests and recurrence.

Keywords: epithelial-to-mesenchymal transition; erdafitinib; immune-checkpoint blocker; infigratinib; miRNA; myeloproliferative syndrome..

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cost-Benefit Analysis
  • Drug Design*
  • Fibroblast Growth Factors / metabolism*
  • Genetic Therapy / methods
  • Humans
  • Molecular Targeted Therapy*
  • Neoplasms / drug therapy
  • Neoplasms / pathology
  • Precision Medicine / economics
  • Precision Medicine / methods
  • Receptors, Fibroblast Growth Factor / metabolism
  • Signal Transduction / drug effects

Substances

  • Receptors, Fibroblast Growth Factor
  • Fibroblast Growth Factors