Combination therapies for targeting FGFR2 fusions in cholangiocarcinoma

Trends Cancer. 2022 Feb;8(2):83-86. doi: 10.1016/j.trecan.2021.11.001. Epub 2021 Nov 25.

Abstract

Fibroblast growth factor receptor 2 (FGFR2) fusion proteins (FFs) are oncogenic drivers in 10-15% of intrahepatic cholangiocarcinoma (iCCA). FGFR-specific inhibitors provide temporary benefit in FF+ unresectable patients. Recent work with mouse iCCA models has documented the necessary role of RAS-ERK downstream to FFs and provided examples of preclinical experimentation aimed at improving FF targeting in iCCA.

Keywords: FGFR tyrosine kinase inhibitors; FGFR2 fusions; intrahepatic cholangiocarcinoma; mouse models of cholangiocarcinoma; resistance to FGFR tyrosine kinase inhibitors; targeted therapies in cholangiocarcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bile Duct Neoplasms* / drug therapy
  • Bile Duct Neoplasms* / genetics
  • Bile Duct Neoplasms* / metabolism
  • Bile Ducts, Intrahepatic / metabolism
  • Bile Ducts, Intrahepatic / pathology
  • Cholangiocarcinoma* / drug therapy
  • Cholangiocarcinoma* / genetics
  • Cholangiocarcinoma* / metabolism
  • Humans
  • Mice
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • Receptor, Fibroblast Growth Factor, Type 2 / genetics
  • Receptor, Fibroblast Growth Factor, Type 2 / therapeutic use

Substances

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