文章：

利用复制应激反应优化癌症治疗

Leveraging the replication stress response to optimize cancer therapy

原文发布日期：2022-11-02

DOI: 10.1038/s41568-022-00518-6

类型: Review Article

开放获取: 否

英文摘要：

High-fidelity DNA replication is critical for the faithful transmission of genetic information to daughter cells. Following genotoxic stress, specialized DNA damage tolerance pathways are activated to ensure replication fork progression. These pathways include translesion DNA synthesis, template switching and repriming. In this Review, we describe how DNA damage tolerance pathways impact genome stability, their connection with tumorigenesis and their effects on cancer therapy response. We discuss recent findings that single-strand DNA gap accumulation impacts chemoresponse and explore a growing body of evidence that suggests that different DNA damage tolerance factors, including translesion synthesis polymerases, template switching proteins and enzymes affecting single-stranded DNA gaps, represent useful cancer targets. We further outline how the consequences of DNA damage tolerance mechanisms could inform the discovery of new biomarkers to refine cancer therapies.

摘要翻译： 

高保真的DNA复制对于遗传信息向子代细胞的准确传递至关重要。在基因毒性应激后，细胞会激活特化的DNA损伤耐受通路以确保复制叉进程，这些通路包括跨损伤DNA合成、模板转换和再引发。本综述将阐述DNA损伤耐受通路如何影响基因组稳定性、其与肿瘤发生的关联以及对癌症治疗反应的影响。我们讨论了最新发现——单链DNA间隙积累会影响化疗反应，并探索了越来越多证据表明不同的DNA损伤耐受因子（包括跨损伤合成聚合酶、模板转换蛋白以及影响单链DNA间隙的酶）可作为有价值的癌症靶点。我们进一步概述了如何利用DNA损伤耐受机制的效应来探索新型生物标志物，以优化癌症治疗方案。

原文链接：

Leveraging the replication stress response to optimize cancer therapy