Division of Cancer Sciences, Faculty of Biology, Medicine and Health, University of Manchester, St Mary's Hospital, Manchester, UK.
Department of Obstetrics and Gynaecology, Manchester Academic Health Science Centre, St Mary's Hospital, Central Manchester NHS Foundation Trust, Manchester Academic Health Science Centre, Level 5, Research, Oxford Road, Manchester, UK.
J Ovarian Res. 2018 Jun 20;11(1):50. doi: 10.1186/s13048-018-0424-x.
Treatment for advanced ovarian cancer is rarely curative; three quarters of patients with advanced disease relapse and ultimately die with resistant disease. Improving patient outcomes will require the introduction of new treatments and better patient selection. Abrogations in the DNA damage response (DDR) may allow such stratifications.A defective DNA-damage response (DDR) is a defining hallmark of high grade serous ovarian cancer (HGSOC). Indeed, current evidence indicates that all HGSOCs harbour a defect in at least one major DDR pathway. However, defective DDR is not mediated through a single mechanism but rather results from a variety of (epi)genetic lesions affecting one or more of the five major DNA repair pathways. Understanding the relationship between these pathways and how these are abrogated will be necessary in order to facilitate appropriate selection of both existing and novel agents.Here we review the current understanding of the DDR with regard to ovarian, and particularly high grade serous, cancer, with reference to existing and emerging treatments as appropriate.
晚期卵巢癌的治疗很少能根治；四分之三的晚期疾病患者会复发，最终死于耐药性疾病。要改善患者的预后，就需要引入新的治疗方法和更好的患者选择。DNA 损伤反应 (DDR) 的缺失可能允许进行这样的分层。
DNA 损伤反应 (DDR) 的缺陷是高级别浆液性卵巢癌 (HGSOC) 的一个明确特征。事实上，目前的证据表明，所有 HGSOC 都至少存在一种主要 DDR 途径的缺陷。然而，DDR 缺陷不是通过单一机制介导的，而是由于影响一种或多种五种主要 DNA 修复途径的多种（表观）遗传损伤导致的。为了促进对现有和新型药物的适当选择，有必要了解这些途径之间的关系以及它们是如何被破坏的。
在这里，我们将参考现有的和新兴的治疗方法，回顾与卵巢癌、特别是高级别浆液性癌相关的 DDR 的现有认识。
