Role of Nucleotide Excision Repair in Cisplatin Resistance.
Role of Nucleotide Excision Repair in Cisplatin Resistance.
复制标题
核苷酸切除修复在顺铂耐药中的作用。
DOI：
10.3390/ijms21239248
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发表时间：
2020-12-04
影响因子：
5.6
通讯作者：
Mao P
中科院分区：
文献类型：
--
作者：
Duan M;Ulibarri J;Liu KJ;Mao P
顺铂是一种用于治疗多种癌症的化疗药物。顺铂的疗效依赖于其与DNA的结合和诱导细胞毒性DNA损伤来杀死癌细胞。以顺铂为基础的治疗以治疗睾丸癌而闻名；然而，用顺铂治疗其他实体瘤并不成功。临床前和临床研究表明，核苷酸切除修复（NER）是肿瘤细胞对顺铂的主要耐药机制。NER是一种多用途的DNA修复系统，针对范围广泛的螺旋扭曲DNA损伤。NER通路由多个步骤组成，包括损伤识别、切口前复合物组装、双切口和修复合成。NER蛋白可以识别顺铂诱导的DNA损伤，并将损伤从基因组中清除，从而中和顺铂的细胞毒性，引起耐药。在这里，我们回顾了NER修复顺铂损伤的分子机制，重点介绍了全基因组顺铂损伤定位方法的最新进展。我们还讨论了关键NER基因的表达和体细胞突变如何影响癌细胞对顺铂的反应。最后，靶向NER因子的小分子为调控癌细胞中的NER能力提供了重要工具。本文将讨论这些抑制剂的研究现状及其在癌症治疗中的意义。
Cisplatin is a chemotherapeutic drug used for the treatment of a number of cancers. The efficacy of cisplatin relies on its binding to DNA and the induction of cytotoxic DNA damage to kill cancer cells. Cisplatin-based therapy is best known for curing testicular cancer; however, treatment of other solid tumors with cisplatin has not been as successful. Pre-clinical and clinical studies have revealed nucleotide excision repair (NER) as a major resistance mechanism against cisplatin in tumor cells. NER is a versatile DNA repair system targeting a wide range of helix-distorting DNA damage. The NER pathway consists of multiple steps, including damage recognition, pre-incision complex assembly, dual incision, and repair synthesis. NER proteins can recognize cisplatin-induced DNA damage and remove the damage from the genome, thereby neutralizing the cytotoxicity of cisplatin and causing drug resistance. Here, we review the molecular mechanism by which NER repairs cisplatin damage, focusing on the recent development of genome-wide cisplatin damage mapping methods. We also discuss how the expression and somatic mutations of key NER genes affect the response of cancer cells to cisplatin. Finally, small molecules targeting NER factors provide important tools to manipulate NER capacity in cancer cells. The status of research on these inhibitors and their implications in cancer treatment will be discussed.
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影响因子：
2.9
作者：
Hey, T;Lipps, G;Krauss, G
通讯作者：
Krauss, G
影响因子：
2.9
作者：
Du P;Wang Y;Chen L;Gan Y;Wu Q
通讯作者：
Wu Q
影响因子：
16
作者：
Coin, Frederic;Oksenych, Valentyn;Egly, Jean-Marc
通讯作者：
Egly, Jean-Marc
DOI：
10.1056/nejmoa1214271
发表时间：
2013-03-21
期刊：
The New England journal of medicine
影响因子：
--
作者：
Friboulet L;Olaussen KA;Pignon JP;Shepherd FA;Tsao MS;Graziano S;Kratzke R;Douillard JY;Seymour L;Pirker R;Filipits M;André F;Solary E;Ponsonnailles F;Robin A;Stoclin A;Dorvault N;Commo F;Adam J;Vanhecke E;Saulnier P;Thomale J;Le Chevalier T;Dunant A;Rousseau V;Le Teuff G;Brambilla E;Soria JC
通讯作者：
Soria JC
影响因子：
16.8
作者：
Damsma, Gerke E.;Alt, Aaron;Cramer, Patrick
通讯作者：
Cramer, Patrick