Nucleosidic DNA demethylating epigenetic drugs - A comprehensive review from discovery to clinic.

摘要: Abstract DNA methylation plays a pivotal role in the etiology of cancer by mediating epigenetic silencing cancer-related genes. Since relationship between aberrant and has been understood, there an explosion research at developing anti-cancer therapies that work inhibiting methylation. From discovery first hypomethylating drugs 1980s to recently discovered second generation pro-drugs, exceedingly large number studies have published describe hypomethylation-based anti-neoplastic action these various stages pre-clinical investigation advanced clinical development. This review is comprehensive report literature past 40 years, on so far nucleosidic inhibitors chronological order. The will provide complete insight readers about mechanisms action, efficacy demethylate re-express genes, anti-tumor activity, cytotoxicity profile, stability, bioavailability drugs. further presents known primary secondary resistance azanucleoside Finally, highlights ubiquitous epi-drugs as chemosensitizers and/or priming agents, recapitulate combinatorial preventive effects with other conventional chemo-drugs, or immunotherapies. analyzes beneficial characteristics drawbacks inhibitors, which assist researchers design future experiments improve therapeutic circumvent challenges path successful therapy.