Research progress of dual inhibitors targeting crosstalk between histone epigenetic modulators for cancer therapy.

Abnormal epigenetics is a critical hallmark of human cancers. Anticancer drug discovery directed at histone epigenetic modulators has gained impressive advances with six drugs available for cancer therapy and numerous other candidates undergoing clinical trials. However, limited therapeutic profile, drug resistance, narrow safety margin, and dose-limiting toxicities pose intractable challenges for their clinical utility. Because histone epigenetic modulators undergo intricate crosstalk and act cooperatively to shape an aberrant epigenetic profile, co-targeting histone epigenetic modulators with a different mechanism of action has rapidly emerged as an attractive strategy to overcome the limitations faced by the single-target epigenetic inhibitors. In this review, we summarize in detail the crosstalk of histone epigenetic modulators in regulating gene transcription and the progress of dual epigenetic inhibitors targeting this crosstalk. [Display omitted] • Histone epigenetic modulators undergo intricate crosstalk and act cooperatively to shape an aberrant epigenetics in cancers. • The crosstalk of histone epigenetic modulators in regulating gene transcription and tumorigenesis is described. • The research progress of dual inhibitors targeting histone epigenetic modulators is summarized. [ABSTRACT FROM AUTHOR]