Selective killing of ATM- or p53-deficient cancer cells through inhibition of ATR
Selective killing of ATM- or p53-deficient cancer cells through inhibition of ATR
复制标题
DOI：
10.1038/nchembio.573
复制
发表时间：
2011-07-01
影响因子：
14.8
通讯作者：
Pollard, John R.
中科院分区：
文献类型：
--
作者：
Reaper, Philip M.;Griffiths, Matthew R.;Pollard, John R.
在这里，我们报告了DNA损伤反应（DDR）激酶ATR的有效和选择性小分子抑制剂的综合生物学特性。我们发现，在dna损伤剂治疗的细胞中，ATR和ATM-p53肿瘤抑制通路之间存在深刻的合成致死相互作用，并建立了ATR抑制作为一种改变电离辐射或基因毒性药物治疗的癌症患者预后的方法。
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.