Platinum resistance: The role of DNA repair pathways
Platinum resistance: The role of DNA repair pathways
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DOI：
10.1158/1078-0432.ccr-07-2238
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发表时间：
2008-03-01
影响因子：
11.5
通讯作者：
Schilder, Russell J.
中科院分区：
文献类型：
--
作者：
Martin, Lainie P.;Hamilton, Thomas C.;Schilder, Russell J.
尽管卡铂、顺铂和奥沙利铂等铂类化疗药物被用于治疗多种恶性疾病，但它们在大多数癌症中的疗效受到耐药性发展的限制。铂耐药有多种因素，但DNA修复过程的改变在介导铂耐药中起重要作用已有一段时间了。最近获得的知识为DNA修复途径的分子机制及其对化疗反应的影响提供了深入的见解。本文将讨论与铂反应有关的最重要的DNA修复途径，即核苷酸切除修复(NER)和错配修复(MMR)，并简要介绍BRCA在DNA修复中的作用。本文将就切除修复交叉互补基因1(ERCC1)缺陷和错配修复缺陷等影响铂类药物疗效的DNA修复改变在恶性肿瘤治疗中的应用进行综述。
Although platinum chemotherapeutic agents such as carboplatin, cisplatin, and oxaliplatin are used to treat a broad range of malignant diseases, their efficacy in most cancers is limited by the development of resistance. There are multiple factors that contribute to platinum resistance but alterations of DNA repair processes have been known for some time to be important in mediating resistance. Recently acquired knowledge has provided insight into the molecular mechanisms of DNA repair pathways and their effect on response to chemotherapy. This review will discuss the most important DNA repair pathways known to be involved in the platinum response, i.e., nucleotide excision repair (NER) and mismatch repair (MMR), and will briefly touch on the role of BRCA in DNA repair. The therapeutic implications of alterations in DNA repair which affect response to platinum in the treatment of patients with malignant disease, such as excision repair cross-complementation group 1 (ERCC1) deficiency and mismatch repair deficiency, will be reviewed.