Modulation of cell death pathways in cancer stem cells: Targeting histone demethylases

Cancer stem cells (CSCs) are tumor initiating cells within the tumor mass; that play a critical role in cancer pathogenesis. CSCs regulate cancer cell survival, metastatic potential, resistance to conventional radio-chemotherapy, disease relapse and poor prognosis. Recent studies have established that the drug resistant cancers and cancer cell lines possess high stem cell like traits compared to their drug sensitive counterparts. Histone demethylases are recently been linked to drug induced reversible tolerant state in cancers. Lysine histone demethylases are enzymes those demethylate lysines in histones and can act as transcriptional repressors or activators. Apart from histones other cellular proteins like E2F1, Rb, STAT3 and p53 are also regulated by methylation and demethylation cycles. In cancer cells these enzymes regulate cell survival, migration, invasion, and proliferation. This review summarizes the current progress of research on the role of histone demethylases in supporting drug tolerant cancer stem cell state and their potential as a drug target.