Role of the EZH2 histone methyltransferase as a therapeutic target in cancer

Pharmacol Ther. 2016 Sep:165:26-31. doi: 10.1016/j.pharmthera.2016.05.003. Epub 2016 May 11.

Abstract

Besides being a genetic disease, cancer is also an epigenetic disease. The histone methyltransferase EZH2 is the catalytic subunit of PRC2, a highly conserved protein complex that regulates gene expression by methylating lysine 27 on histone H3. Given its role in tumorigenesis and its prognostic value in several tumor types, this protein appears a relevant therapeutic target. This review focuses on the preclinical and preliminary clinical results of studies investigating EZH2 inhibitors in human malignancies. These emerging data suggest that EZH2 inhibitors represent a very promising class of drugs, which will probably have a major impact on improving outcome and reducing toxicity for patients with indolent and aggressive B-cell lymphomas and other specific solid tumors.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Biomarkers, Tumor / antagonists & inhibitors*
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Drug Design*
  • Drug Resistance, Neoplasm
  • Enhancer of Zeste Homolog 2 Protein / antagonists & inhibitors*
  • Enhancer of Zeste Homolog 2 Protein / genetics
  • Enhancer of Zeste Homolog 2 Protein / metabolism
  • Enzyme Inhibitors / adverse effects
  • Enzyme Inhibitors / therapeutic use*
  • Humans
  • Molecular Targeted Therapy
  • Neoplasms / drug therapy*
  • Neoplasms / enzymology
  • Neoplasms / genetics
  • Neoplasms / pathology
  • Signal Transduction / drug effects

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Enzyme Inhibitors
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein