Histone Demethylase Modulation: Epigenetic Strategy to Combat Cancer Progression

Abstract

Epigenetic modifications are heritable, reversible changes in histones or the DNA that control gene functions, being exogenous to the genomic sequence itself. Human diseases, particularly cancer, are frequently connected to epigenetic dysregulations. One of them is histone methylation, which is a dynamically reversible and synchronously regulated process that orchestrates the three-dimensional epigenome, nuclear processes of transcription, DNA repair, cell cycle, and epigenetic functions, by adding or removing methylation groups to histones. Over the past few years, reversible histone methylation has become recognized as a crucial regulatory mechanism for the epigenome. With the development of numerous medications that target epigenetic regulators, epigenome-targeted therapy has been used in the treatment of malignancies and has shown meaningful therapeutic potential in preclinical and clinical trials. The present review focuses on the recent advances in our knowledge on the role of histone demethylases in tumor development and modulation, in emphasizing molecular mechanisms that control cancer cell progression. Finally, we emphasize current developments in the advent of new molecular inhibitors that target histone demethylases to regulate cancer progression.

Degraders in epigenetic therapy: PROTACs and beyond

“…Lysine demethylase 5C (KDM5C), alternatively referred to as JARID1C or SMCX, serves as a demethylase specifically targeting H3K4me2/3 in mammalian cells 179 . KDM5C is widely acknowledged as a tumor suppressor due to its role in modulating enhancer activities across multiple cancer types, including prostate, breast, cervix, and clear-cell renal carcinoma 180 . Despite some RNA interference (RNAi) experiments, which indicated that KDM5C defects exhibited anticancer effects, the efficacies of several reported KDM5C inhibitors for exerting potent anticancer effects remain limited 181 .…”