Histone-modifying Enzymes as Therapeutic Targets in Glioma: Biological Rationale and Translational Findings.

Abstract

Histone-modifying enzymes have emerged as therapeutic targets in glioma, particularly H3K27M-altered diffuse midline glioma. This article reviews the biological rationale for targeting these enzymes and summarizes the current preclinical and clinical evidence for histone deacetylase, methyltransferase, and demethylase inhibitors. It also discusses the utility of nonenzymatic agents, including bromodomain and extraterminal inhibitors and dordaviprone, that have achieved similar epigenetic effects in this disease.