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Comment
. 2022 Feb 1;82(3):359-361.
doi: 10.1158/0008-5472.CAN-21-4311.

EZH2 Inhibitors: The Unpacking Revolution

Vera Adema  1 , Simona Colla  2
Affiliations
Comment

EZH2 Inhibitors: The Unpacking Revolution

Vera Adema et al. Cancer Res. .

Abstract

The methylation of lysine 27 on histone H3 (H3K27me3) is a chromatin mark associated with nucleosome condensation and gene expression silencing. EZH2 is a lysine methyltransferase that catalyzes H3K27me3. In this issue of Cancer Research, Porazzi and colleagues report that pretreatment with EZH2 inhibitors opened up the H3K27me3-marked chromatin of acute myeloid leukemia (AML) cells, which enhanced DNA damage and apoptosis induced by chemotherapeutic agents, in particular the topoisomerase II inhibitors, doxorubicin and etoposide. The EZH2 inhibitor/doxorubicin combination also enabled the expression of proapoptotic genes, potentially contributing to the death of AML cells. This study has significant implications for improving the efficacy of DNA-damaging cytotoxic agents in AML, thereby enabling lower chemotherapy doses and reducing treatment-related side effects.See related article by Porazzi et al., p. 458.

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References

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