Targeting EZH2 for cancer therapy: From current progress to novel strategies.

Abstract

EZH2, the catalytic subunit of PRC2, catalyzes histone H3 lysine 27 (H3K27) trimethylation to induce the agglutination of chromosomes and in turn represses the transcription of the target genes. Numerous reports indicate that EZH2 is overexpressed in a variety of malignant tumor tissues. Therefore, targeting EZH2 protein is a promising strategy for cancer treatment. So far, many small molecule EZH2 specific inhibitors have entered clinical trials, but many of them harbored limited clinical efficacy. New technologies and methods are imperative to enhance the anticancer activity of EZH2. In this review, the structure and biological functions of EZH2 protein will be reviewed. The internal relationship between EZH2 and various diseases will be expounded. The development status of specific inhibitors for EZH2, and the latest progress of new strategies such as drug combination, dual-target inhibitors, targeted protein degradation technology and protein-protein interactions (PPI) inhibitors will be emphatically summarized and analyzed.

• Authors: Jia Zeng, Jifa Zhang, Ying Sun, Jiaxing Wang, Changyu Ren, Souvik Banerjee, Liang Ouyang, Yuxi Wang
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 238 Pg. 114419 (Aug 05 2022) ISSN: 1768-3254 [Electronic] France
• PMID: 35569264 (Publication Type: Journal Article, Review)
• Copyright: Copyright © 2022 Elsevier Masson SAS. All rights reserved.

Chemical References

• Enzyme Inhibitors
• EZH2 protein, human
• Enhancer of Zeste Homolog 2 Protein

Topics

• Catalytic Domain
• Enhancer of Zeste Homolog 2 Protein (metabolism)
• Enzyme Inhibitors (therapeutic use)
• Humans
• Neoplasms (metabolism)