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

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15110%2F18%3A73590597" target="_blank" >RIV/61989592:15110/18:73590597 - isvavai.cz</a>

Result on the web

<a href="http://dx.doi.org/10.1016/j.pharmthera.2018.02.006" target="_blank" >http://dx.doi.org/10.1016/j.pharmthera.2018.02.006</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.pharmthera.2018.02.006" target="_blank" >10.1016/j.pharmthera.2018.02.006</a>

Result language

angličtina

Original language name

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

Original language description

DNA methylation plays a pivotal role in the etiology of cancer by mediating epigenetic silencing of cancer-related genes. Since the relationship between aberrant DNA methylation and cancer has been understood, there has been an explosion of research at developing anti-cancer therapies that work by inhibiting DNA methylation. From the discovery of first DNA hypomethylating drugs in the 1980s to recently discovered second generation pro-drugs, exceedingly large number of studies have been published that describe the DNA hypomethylation-based antineoplastic action of these drugs in various stages of the pre-clinical investigation and advanced stages of clinical development. This review is a comprehensive report of the literature published in past 40 years, on so far discovered nucleosidic DNA methylation inhibitors in chronological order. The review will provide a complete insight to the readers about the mechanisms of action, efficacy to demethylate and re-express various cancer related genes, anti-tumor activity, cytotoxicity profile, stability, and bioavailability of these drugs. The review further presents the far known mechanisms of primary and secondary resistance to azanucleoside drugs. Finally, the review highlights the ubiquitous role of DNA hypomethylating epi-drugs as chemosensitizers and/or priming agents, and recapitulate the combinatorial cancer preventive effects of these drugs with other epigenetic agents, conventional chemo-drugs, or immunotherapies. This comprehensive review analyzes the beneficial characteristics and drawbacks of nucleosidic DNA methylation inhibitors, which will assist the pre-clinical and clinical researchers in the design of future experiments to improve the therapeutic efficacy of these drugs and circumvent the challenges in the path of successful epigenetic therapy. (C) 2018 The Authors. Published by Elsevier Inc.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30104 - Pharmacology and pharmacy

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2018

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

PHARMACOLOGY &amp; THERAPEUTICS

ISSN

0163-7258

e-ISSN

—

Volume of the periodical

188

Issue of the periodical within the volume

AUG 2018

Country of publishing house

GB - UNITED KINGDOM

Number of pages

35

Pages from-to

45-79

UT code for WoS article

000441489000005

EID of the result in the Scopus database

2-s2.0-85043342854