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

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. [Display omitted] •EZH2 plays a vital role in the development of several human cancers.•Inhibition of EZH2 is a promising strategy for the treatment of various diseases, especially malignant tumors.•Guiding for future drug modification and design of EZH2 inhibitors.•Emerging therapeutic technologies targeting EZH2 are discussed and prospected.