Lysine demethylases 6 A and 6B as epigenetic regulators in therapeutic resistance of cancer.

Histone 3 lysine 27 (H3K27) demethylation is a key post-translational modification of chromatin and plays a fundamental role in gene activation. Demethylation of H3K27 is mediated by Jumonji C domain-containing lysine demethylase 6 A (KDM6A) and its paralog, KDM6B, both of which are responsible for homeostasis, autoimmune response, infectious diseases, and cancers. To date, mounting studies dedicate the roles of KDM6A/B on tumor promotion or suppression, and there are many reviews systematically summarize the relevant mechanisms of KDM6A/B in tumor development and therapy. KDM6A and KDM6B also contribute to the regulation of therapeutic insensitivity to chemotherapy, targeted response, radiotherapy and immunotherapy. Herein, we outline the current knowledge of KDM6A/B in regulation of therapeutic resistance, and suggest that KDM6A/B holds immense potential in recovering therapeutic resistance.