全部 标题 作者
关键词 摘要

OALib Journal期刊
ISSN: 2333-9721
费用:99美元

查看量下载量

相关文章

更多...

Pharmacokinetic and pharmacodynamic analysis of 5-aza-2’-deoxycytidine (decitabine) in the design of its dose-schedule for cancer therapy

DOI: 10.1186/1868-7083-5-3

Keywords: Decitabine, 5-aza-2’-deoxycytidine, Epigenetics, AML, MDS, DNA methylation, Pharmacokinetics, Pharmacodynamics

Full-Text   Cite this paper   Add to My Lib

Abstract:

5-Aza-2′-deoxycytidine (5-AZA-CdR, decitabine) was first synthesized in 1964 by Pliml and Sorm [1] and its potential activity in leukemia was reported in 1968 by Sorm and Vesely [2]. 5-AZA-CdR is an analog of the natural nucleoside 2′-deoxycytidine in which the carbon in the 5-position of the cytosine is replaced by nitrogen. Preclinical studies in rodents indicated that 5-AZA-CdR is a more potent antileukemic agent than cytosine arabinoside (ARA-C) [3,4]. In 1979, Taylor and Jones [5] reported that 5-AZA-CdR could induce cells in culture to differentiate into different phenotypes and this activity correlated with its inhibition of DNA methylation. The first review on the pharmacologic properties of 5-AZA-CdR was published in 1979 [6] and the first clinical trial on 5-AZA-CdR in patients with acute leukemia was published in 1981 [7].Although the unique demethylating capacity of 5-AZA-CdR has been known for many years, its approval for the treatment of cancer took a long time, perhaps due to a lack of understanding of the importance of epigenetic changes in malignancy during the early years of development [8]. 5-AZA-CdR was approved for the treatment of myelodysplastic syndrome (MDS) in 2006 and shows anti-leukemic activity against acute myeloid leukemia (AML) as well [8,9]. Its clinical activity against solid tumors is under investigation. 5-AZA-CdR also displays some effectiveness in the treatment of sickle cell disease, which is nonmalignant [10]. Low-dose 5-AZA-CdR was proposed to be effective for treating MDS due to its epigenetic action, whereas higher doses were too toxic due the poor hematologic status of these patients [11]. The objectives of this review is to analyze preclinical and clinical data on 5-AZA-CdR and develop a rationale for optimization of its dose schedule for the treatment of cancer.Recent progress on elucidating the important role of epigenetics in the development of malignancy has generated more interest in the chemotherapeutic potential of

Full-Text

Contact Us

service@oalib.com

QQ:3279437679

WhatsApp +8615387084133