Fibroblast Growth Factor Receptors: From the Oncogenic Pathway to Targeted Therapy

Curr Mol Med. 2016;16(1):40-62. doi: 10.2174/1566524016666151222144231.

Abstract

The family of fibroblast growth factor (FGFs) and their receptors (FGFRs) regulates vital roles in many biological processes affecting cell proliferation, migration, differentiation and survival. Deregulation of the FGF/FGFR signaling pathway in cancers has been better understood and the main molecular mechanisms responsible for the activation of this pathway are gene mutations, gene fusions and gene amplification. DNA and RNA-based technologies have been used to detect these abnormalities, especially in FGFR1, FGFR2 and FGFR3 and tests have been developed for their detection, but no assay has been proved ideal for molecular diagnosis. Interestingly, the increase in the molecular biology knowledge has supported and assisted the development of therapeutic drugs targeting the most important components of this pathway. Multi- and selective tyrosine kinase inhibitors (TKIs) as well as monoclonal antibodies anti-FGFR are under investigation in preclinical and clinical trials. In this article, we reviewed those aspects with special emphasis on the pathway genomic alterations related to solid tumors, and the molecular diagnostic assays potentially able to stratify patients for the treatment with FGFR TKIs.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Carcinogenesis / drug effects
  • Carcinogenesis / genetics*
  • Fibroblast Growth Factors / genetics*
  • Humans
  • Mutation / drug effects
  • Mutation / genetics
  • Neoplasms / drug therapy*
  • Neoplasms / genetics*
  • Receptor, Fibroblast Growth Factor, Type 2 / genetics*
  • Signal Transduction / drug effects
  • Signal Transduction / genetics*

Substances

  • Antineoplastic Agents
  • Fibroblast Growth Factors
  • Receptor, Fibroblast Growth Factor, Type 2