作者
Reda Z Mahfouz, Ania Jankowska, Quteba Ebrahem, Xiaorong Gu, Valeria Visconte, Ali Tabarroki, Pramod Terse, Joseph Covey, Kenneth Chan, Yonghua Ling, Kory J Engelke, Mikkael A Sekeres, Ramon Tiu, Jaroslaw Maciejewski, Tomas Radivoyevitch, Yogen Saunthararajah
发表日期
2013/2/15
期刊
Clinical cancer research
卷号
19
期号
4
页码范围
938-948
出版商
American Association for Cancer Research
简介
Purpose: The cytidine analogs 5-azacytidine and decitabine, used to treat myelodysplastic syndromes (MDS), produce a molecular epigenetic effect, depletion of DNA-methyltransferase 1 (DNMT1). This action is S-phase dependent. Hence, genetic factors that decrease the half-lives of these drugs could impact efficacy. Documentation of such impact, and elucidation of underlying mechanisms, could lead to improved clinical application.
Experimental design: Cytidine deaminase (CDA) rapidly inactivates 5-azacytidine/decitabine. The effect of CDA SNP A79C and gender on CDA expression, enzyme activity, and drug pharmacokinetics/pharmacodynamics was examined in mice and humans, and the impact on overall survival (OS) was evaluated in 5-azacytidine/decitabine-treated patients with MDS (n = 90) and cytarabine-treated patients with acute myeloid leukemia (AML) (n = 76 …
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RZ Mahfouz, A Jankowska, Q Ebrahem, X Gu… - Clinical cancer research, 2013