Drugging histone methyltransferases in cancer

Curr Opin Chem Biol. 2020 Jun:56:51-62. doi: 10.1016/j.cbpa.2019.11.009. Epub 2020 Jan 23.

Abstract

Targeting chromatin-modifying enzymes is a promising strategy for cancer treatment. The antitumor effectivity of compounds inhibiting histone methyltransferases - mainly EZH2 - is currently being tested in phase I/II clinical trials, some of them showing positive results in hematological malignancies and solid tumors of specific mutational background. In this review, we aim at highlighting the recent advances in the field of histone methyltransferase inhibitors and describing the challenges that need to be addressed for their successful implementation in the clinics.

Keywords: Cancer; EZH2; Epidrugs; Histone methyltransferases; PRC2.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology
  • Carcinogenesis / metabolism
  • Chromatin / genetics
  • Chromatin / metabolism
  • Drug Design
  • Drug Therapy, Combination
  • Enhancer of Zeste Homolog 2 Protein / metabolism
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology
  • Gene Expression Regulation
  • Histone Methyltransferases / antagonists & inhibitors*
  • Humans
  • Methylation
  • Mutation
  • Neoplasms / drug therapy*

Substances

  • Antineoplastic Agents
  • Chromatin
  • Enzyme Inhibitors
  • Histone Methyltransferases
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein