Genetic Impairments of PRC2 Activity in Oncology: Problems and Prospects

PRC2 (Polycomb repressive complex 2) is a conserved protein complex in multicellular organisms that is required to maintain gene repression. The catalytic subunit of PRC2, the EZH2 protein, provides the methylation of histone H3K27 (H3K27me1/2/3). It was demonstrated that a number of human cancers were associated with overexpression of PRC2 subunits, as well as with mutations that enhanced the EZH2 catalytic activity. At the same time, a group of cancers correlate with mutations that inhibit PRC2. A number of small molecule inhibitors to the PRC2 subunits have been developed, primarily to EZH2. One of these, tazemetostat, received approval in January 2020 in the United States for the treatment of epithelioid sarcoma. This review focuses on the role of PRC2 in cancer development and summarizes information on the designed PRC2 inhibitors.