Precision Oncology for Hepatocellular Cancer: Slivering the Liver by FGF19-FGF4-KLB Pathway Inhibition

Cancer Discov. 2019 Dec;9(12):1646-1649. doi: 10.1158/2159-8290.CD-19-1156.

Abstract

This issue reports two studies, one by Hatlen and colleagues and the other by Kim and colleagues, that detail the drug-development journey of the FGFR19-FGFR4 inhibitor fisogatinib (BLU-554), from identification of the drug to preclinical validation studies to finally the results of the proof-of-concept first-in-human phase I trial of this potent and selective, type I irreversible inhibitor of FGFR4. Moreover, Hatlen and colleagues also report a resistance mechanism acquired after therapy that targets selective FGF4 inhibition, which validates FGF as a specific target in hepatocellular cancer.See related article by Hatlen et al., p. 1686.See related article by Kim et al., p. 1696.

Publication types

  • Comment

MeSH terms

  • Carcinoma, Hepatocellular*
  • Fibroblast Growth Factor 4
  • Fibroblast Growth Factors
  • Humans
  • Klotho Proteins
  • Liver Neoplasms*
  • Membrane Proteins
  • Precision Medicine
  • Protein Kinase Inhibitors
  • Receptor, Fibroblast Growth Factor, Type 4

Substances

  • FGF19 protein, human
  • FGF4 protein, human
  • Fibroblast Growth Factor 4
  • KLB protein, human
  • Membrane Proteins
  • Protein Kinase Inhibitors
  • Fibroblast Growth Factors
  • FGFR4 protein, human
  • Receptor, Fibroblast Growth Factor, Type 4
  • Klotho Proteins