Investigational fibroblast growth factor receptor 2 antagonists in early phase clinical trials to treat solid tumors

Expert Opin Investig Drugs. 2019 Oct;28(10):903-916. doi: 10.1080/13543784.2019.1672655. Epub 2019 Oct 4.

Abstract

Introduction: Fibroblast growth factor receptor 2 (FGFR2) is a highly conserved transmembrane tyrosine kinase receptor. FGFR2 dysregulation occurs in numerous human solid tumors and overexpression is closely associated with tumor progression. FGFR2 has recently been reported as a therapeutic target for cancer. Several targeted therapies are being investigated to disrupt FGFR2 activity; these include multi-target tyrosine kinase inhibitors (TKIs), pan-FGFR targeted TKIs and FGFR2 monoclonal antibodies. Areas: This review examines FGFR2 regulation and function in cancer and its potential as a target for cancer treatment. Expert opinion: Highly specific FGFR2 blockers have not yet been developed and moreover, resistance to FGFR2-targeted therapies is a challenge. More sophisticated patient selection strategies would help improve FGFR2-targeted therapies and combination therapy is considered the most promising approach for cancer patients with FGFR2 alterations.

Keywords: FGFR-target TKIs; Fibroblast growth factor receptor 2 (FGFR2); antibody; multi-target tyrosine kinase inhibitors (TKIs); solid tumor.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacology
  • Drug Resistance, Neoplasm
  • Humans
  • Molecular Targeted Therapy
  • Neoplasms / drug therapy*
  • Neoplasms / pathology
  • Patient Selection
  • Protein Kinase Inhibitors / administration & dosage*
  • Protein Kinase Inhibitors / pharmacology
  • Receptor, Fibroblast Growth Factor, Type 2 / antagonists & inhibitors*

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • FGFR2 protein, human
  • Receptor, Fibroblast Growth Factor, Type 2