FGF2: a novel druggable target for glioblastoma?

Expert Opin Ther Targets. 2020 Apr;24(4):311-318. doi: 10.1080/14728222.2020.1736558. Epub 2020 Mar 16.

Abstract

Introduction: Fibroblast growth factors (FGFs) are key mitogens in tissue homeostasis and cancer. FGF2 regulates self-renewal of multiple stem-cell types, is widely used in stem cell culture paradigms and has been adopted for cultivating the growth of cancer stem cells ex vivo. Research has shed light on the functions of FGF2 in brain tumors, particularly malignant glioma, and this has demonstrated that FGF2 increases self-renewal of glioblastoma stem cells.Areas covered: This review examines the potential targeting of FGF2 signaling as a possible treatment avenue for glioblastoma. The expression of FGF ligands and the FGFR family of receptor tyrosine kinases in the normal brain and in glioblastoma is described. Moreover, the paper sheds light on FGF/FGFR signaling, including the function of heparin/heparan sulfate proteoglycans in facilitating FGF signaling. We speculate on potential avenues for the therapeutic targeting of the FGF2-FGF receptor signaling axis in glioblastoma and the associated challenges envisioned with these approaches.Expert opinion: Precision targeting of FGF/FGFR signaling could improve prospective glioblastoma therapeutics and moderate adverse effects. Shrewd development of experimental models and FGF2 inhibitors could provide a 'pharmacological toolbox' for targeting diverse ligand/receptor combinations.

Keywords: FGF; FGF2; Fibroblast growth factor; brain cancer; drug target; glioblastoma; glioma.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / genetics
  • Brain Neoplasms / pathology
  • Fibroblast Growth Factor 2 / genetics*
  • Glioblastoma / drug therapy*
  • Glioblastoma / genetics
  • Glioblastoma / pathology
  • Humans
  • Molecular Targeted Therapy
  • Neoplastic Stem Cells
  • Signal Transduction / drug effects

Substances

  • Antineoplastic Agents
  • Fibroblast Growth Factor 2