The Targeted Inhibition of Histone Lysine Demethylases as a Novel Promising Anti-Cancer Therapeutic Strategy-An Update on Recent Evidence.

A growing body of evidence confirms that non-mutational epigenetic reprogramming constitutes an important hallmark of cancer, contributing to the heterogeneity and phenotypic plasticity observed in cancers. Among the many epigenetic modulators, histone lysine demethylases (KDMs) have emerged as promising targets for pharmacological inhibition in cancer treatment. KDMs were found to be frequently overexpressed and/or hyperactivated in cancer cells, and their inhibition was shown to result in the inhibition of cancer cell growth both in vitro and in vivo. The inhibition of Lysine-specific histone demethylase 1A (LSD1), KDM3, KDM4, KDM5, and KDM6 may affect cell survival, proliferation, motility, and apoptosis induction. Importantly, KDM inhibitors can be used as modulators of anti-cancer immune response and sensitivity to radiation and chemotherapy. This narrative review aims to present the most recent evidence documenting the anti-cancer potential of KDM inhibitors.