文章：

PARP抑制剂在卵巢癌中的策略性应用与优化管理

PARP Inhibitors: Strategic Use and Optimal Management in Ovarian Cancer

原文发布日期：25 February 2024

DOI: 10.3390/cancers16050932

类型: Article

开放获取: 是

英文摘要：

Poly (ADP-ribose) polymerase (PARP) inhibitors have become an established part of the anticancer armamentarium. Discovered in the 1980s, PARP inhibitors (PARPis) were initially developed to exploit the presence of BRCA mutations, which disrupt the homologous recombination repair of deoxyribonucleic acid (DNA) via synthetic lethality, an intrinsic vulnerability caused by the cell’s dependence on other DNA repair mechanisms for which PARP is an essential contributor. PARPi use expanded with the demonstration of clinical benefit when other mechanisms of high-fidelity DNA damage response were present in cancer cells called homologous repair deficiency (HRD). Recently, new data have resulted in the voluntary withdrawal of later-line treatment indications for all the available PARPis used in ovarian cancer because of a negative impact on overall survival (OS). PARPi switch maintenance to consolidate a response to platinum-based therapy is recommended for earlier treatment lines to have the greatest impact on the chance of cure and length of survival. This article reviews the clinical utility of PARPis and how to integrate them into best practices.

摘要翻译： 

聚腺苷二磷酸核糖聚合酶（PARP）抑制剂已成为抗癌药物库中的重要组成部分。PARP抑制剂于20世纪80年代被发现，最初旨在利用BRCA基因突变，通过合成致死机制破坏脱氧核糖核酸（DNA）的同源重组修复——这种内在脆弱性源于细胞对其他DNA修复机制的依赖，而PARP在其中发挥关键作用。随着研究发现癌细胞中存在同源修复缺陷（HRD）等高保真DNA损伤应答机制可带来临床获益，PARP抑制剂的应用范围得以拓展。近期新数据显示，由于对总生存期（OS）产生负面影响，所有用于卵巢癌治疗的PARP抑制剂已自愿撤回后线治疗适应症。为最大程度提高治愈机会并延长生存时间，建议在早期治疗线序中采用PARP抑制剂转换维持治疗，以巩固铂类化疗的应答效果。本文综述了PARP抑制剂的临床应用价值及其在最佳实践中的整合策略。

原文链接：

PARP Inhibitors: Strategic Use and Optimal Management in Ovarian Cancer