DNA repair and synthetic lethality.
DNA repair and synthetic lethality.
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DNA修复和合成致死
DOI：
10.4248/ijos11064
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发表时间：
2011-10
影响因子：
14.9
通讯作者：
Powell SN
中科院分区：
文献类型：
--
作者：
Guo GS;Zhang FM;Gao RJ;Delsite R;Feng ZH;Powell SN
肿瘤通常有DNA修复缺陷，这表明肿瘤中其他DNA修复途径的额外抑制可能会导致合成致命性。越来越多的数据表明，DNA修复缺陷肿瘤，特别是同源重组(HR)，对DNA损伤剂高度敏感。因此，HR缺陷肿瘤对合成致死性方法表现出潜在的脆弱性，这可能导致新的治疗策略。众所周知，多聚腺二磷酸核糖聚合酶(PARP)抑制剂在BRCA1或BRCA2基因缺陷的肿瘤中显示出合成的致命效应，而BRCA1或BRCA2基因编码的蛋白质是有效的HR所必需的。在这篇综述中，我们总结了靶向DNA修复途径和其他DNA代谢功能的策略，以导致HR缺陷肿瘤细胞的合成杀伤力。
Tumors often have DNA repair defects, suggesting additional inhibition of other DNA repair pathways in tumors may lead to synthetic lethality. Accumulating data demonstrate that DNA repair-defective tumors, in particular homologous recombination (HR), are highly sensitive to DNA-damaging agents. Thus, HR-defective tumors exhibit potential vulnerability to the synthetic lethality approach, which may lead to new therapeutic strategies. It is well known that poly (adenosine diphosphate (ADP)-ribose) polymerase (PARP) inhibitors show the synthetically lethal effect in tumors defective in BRCA1 or BRCA2 genes encoded proteins that are required for efficient HR. In this review, we summarize the strategies of targeting DNA repair pathways and other DNA metabolic functions to cause synthetic lethality in HR-defective tumor cells.