Selective killing of ATM- or p53-deficient cancer cells through inhibition of ATR

被引：0
|
作者：
Reaper, Philip M. [1 ]
Griffiths, Matthew R. [1 ]
Long, Joanna M. [1 ]
Charrier, Jean-Damien [1 ]
MacCormick, Somhairle [1 ]
Charlton, Peter A. [1 ]
Golec, Julian M. C. [1 ]
Pollard, John R. [1 ]
机构：
[1] Vertex Pharmaceut Europe, Abingdon, Oxon, England
来源：
NATURE CHEMICAL BIOLOGY | 2011年 / 7卷 / 07期
关键词：
DOUBLE-STRAND BREAKS; DNA-DAMAGE RESPONSE; LUNG-CANCER; CISPLATIN; ACTIVATION; CARCINOMA; CHROMATIN; REPAIR; MODEL; CHK2;
D O I：
10.1038/NCHEMBIO.573
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Here we report a comprehensive biological characterization of a potent and selective small-molecule inhibitor of the DNA damage response (DDR) kinase ATR. We show a profound synthetic lethal interaction between ATR and the ATM-p53 tumor suppressor pathway in cells treated with DNA-damaging agents and establish ATR inhibition as a way to transform the outcome for patients with cancer treated with ionizing radiation or genotoxic drugs.
引用
收藏
页码：428 / 430
页数：3
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