School of Public Health, Shandong University, Jinan 250012, China.
Int J Oral Sci. 2011 Oct;3(4):176-9. doi: 10.4248/IJOS11064.
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.
肿瘤通常存在 DNA 修复缺陷，提示针对肿瘤中其他 DNA 修复途径的进一步抑制可能导致合成致死。越来越多的数据表明，DNA 修复缺陷的肿瘤，特别是同源重组 (HR)，对 DNA 损伤剂高度敏感。因此，HR 缺陷型肿瘤对合成致死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，聚 (腺苷二磷酸核糖) 聚合酶 (PARP) 抑制剂在 BRCA1 或 BRCA2 基因编码的蛋白缺陷的肿瘤中表现出合成致死效应，这些蛋白是有效 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 代谢功能以在 HR 缺陷型肿瘤细胞中引起合成致死的策略。
