PARP抑制剂在卵巢癌中的应用及耐药机制研究  

Application and Drug Resistance Mechanism of PARP Inhibitors in the treatment of Ovarian Cancer

作　　者：曹静[1] 唐喆[1] 童鑫[1] 帅维维[1] CAO Jing;TANG Zhe;TONG Xin;SHUAI Weiwei(Department of Pharmacy,Women's Hospital of Nanjing Medical University,Nanjing Women and Children's Healthcare Hospital,Nanjing 210004,Jiangsu Province,China)

机构地区：[1]南京医科大学附属妇产医院(南京市妇幼保健院)药学部,江苏南京210004

出　　处：《肿瘤》2024年第4期432-441,共10页Tumor

摘　　要：卵巢癌是妇科肿瘤中致死率较高的恶性肿瘤之一。卵巢癌通常表现出基因组不稳定性,约有50%的卵巢癌存在一种或多种DNA修复途径缺陷,且大多数在同源重组途径中。聚腺苷二磷酸核糖聚合酶(poly ADP-ribose polymerase,PARP)抑制剂可抑制DNA修复途径并引起肿瘤细胞凋亡,尤其在同源重组缺陷的细胞中。越来越多的研究显示,PARP抑制剂在治疗同源重组缺陷型卵巢癌方面已取得显著的疗效,因此本文总结了PARP抑制剂的作用机制以及几种PARP抑制剂的临床研究结果,同时对PARP抑制剂的耐药机制进行了综述。笔者认为克服PARP抑制剂耐药,寻找提高其敏感性的可行性策略将是目前的研究热点。Ovarian cancer is one of the more lethal malignancies among gynaecological tumours.Ovarian cancer usually exhibits genomic instability,and about 50%of ovarian cancers have defects in one or more DNA repair pathways,mostly in the homologous recombination pathway.Inhibitors of poly ADP-ribose polymerase(PARP)inhibit DNA repair pathways and cause apoptosis in tumour cells,especially in cells defective in homologous recombination.More and more studies have shown that PARP inhibitors have achieved significant efficacy in the treatment of homologous recombination-deficient ovarian cancer,so this paper summarises the mechanism of action of PARP inhibitors and the results of clinical studies of several PARP inhibitors,as well as an overview of the resistance mechanism of PARP inhibitors.The author believes that overcoming PARP inhibitor resistance and finding feasible strategies to improve its sensitivity will be the current research hotspot.

关 键 词：卵巢癌 PARP抑制剂 作用机制 耐药机制 逆转策略 

分 类 号：R737.31[医药卫生—肿瘤]