Targeting WNT/β-Catenin via Modulating EZH2 Function: A New Chapter in the Treatment of β-Catenin Mutant Hepatocellular Carcinoma?

Cancer Res. 2023 Nov 1;83(21):3498-3500. doi: 10.1158/0008-5472.CAN-23-2921.

Abstract

In a recent study, Rialdi and colleagues identified a specific vulnerability in β-catenin mutant hepatocellular carcinoma (HCC) via EZH2-mediated suppression of WNT signaling and revealed the selective anti-HCC activity of WNTinib, a chemical derivative of regorafenib and sorafenib in targeting this vulnerability. Their discoveries highlight the role of EZH2 in modulating WNT signaling and suggest an implication of WNTinihb as a small-molecule inhibitor for the treatment of HCC with activated WNT/β-catenin.

Publication types

  • Research Support, N.I.H., Intramural
  • Comment

MeSH terms

  • Carcinoma, Hepatocellular* / drug therapy
  • Carcinoma, Hepatocellular* / genetics
  • Carcinoma, Hepatocellular* / pathology
  • Cell Line, Tumor
  • Cell Proliferation
  • Enhancer of Zeste Homolog 2 Protein / genetics
  • Enhancer of Zeste Homolog 2 Protein / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Liver Neoplasms* / drug therapy
  • Liver Neoplasms* / genetics
  • Liver Neoplasms* / pathology
  • Wnt Signaling Pathway
  • beta Catenin / genetics
  • beta Catenin / metabolism

Substances

  • beta Catenin
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein