EZH2 methyltransferase as a therapeutic target in hematological malignancies

Abstract

EZH2 methyltransferase is the subunit of the PRC2 complex that catalyzes tri-methylation of histone H3 at Lys 27 (H3K27me3). EZH2 is one of the Polycomb proteins that are the main epigenetic factors and are responsible for silencing and inactivating genes. This enzyme has a dual function in cancer - it is an oncogene and a suppressor gene. Abnormalities resulting from overexpression or mutation in EZH2 coding genes have been found in patients suffering from hematological malignancies and solid cancers. Therefore, it is necessary to treat these patients, has begun studies on molecules directed against the PRC2 complex, in particular against EZH1/EZH2. In 2012, a breakthrough in the development of targeted therapy with inhibitors of methyltransferase EZH2 has been the discovery of highly selective compounds containing the 2-pyridine in their chemical structure. In this review, draws attention to the latest findings regarding the oncogenic functions of EZH2 methyltransferase and their impact on the development of tumors. In addition, the text contains current information about preclinical and clinical trials on EZH2 inhibitors testing mainly in hematological cancers.