Musella A, Marchetti C, Gasparri M L, Salerno L, Casorelli A, Domenici L, Imperiale L, Ruscito I, Abdul Halim T, Palaia I, Di Donato V, Pecorini F, Monti M, Muzii L, Panici P B
University Sapienza of Rome Department of Gynecology, Obstetrics and Urological Sciences Rome Italy.
University Sapienza of Rome Department of Gynecology, Obstetrics and Urological Sciences Rome Italy marialuisa.gasparri@uniroma1.it.
Cell Mol Biol (Noisy-le-grand). 2015 Oct 30;61(6):44-61.
Ovarian cancer is burdened by the highest mortality rate among gynecological cancers. Gold standard is represented by the association of platinum-taxane -based chemotherapy and radical surgery. Despite several adjustments occurred in cytotoxic drug in last decades, most patients continue to relapse, and no significant enhancement has been reached in the overall survival. The development of drug resistance and the recurrence of disease have prompted the investigations of other targets that can be used in the treatment of ovarian cancers. Among such targets, polyadenosine diphosphate-ribose polymerase (PARP) represents a novel way to target specific patways involved in tumor growth. PARP accelerates the reaction of the polyADP-ribosylation of proteins implicated in DNA repair. PARP inhibitors have shown activity in cancers with BRCA mutations, with other deficient DNA repair genes or signaling pathways that modulate DNA repair, or in association with DNA damaging agents not involved in DNA repair dysfunction. A number of inhibitors for PARP has been developed, and such drugs are under investigation in clinical trials to identify their impact in the treatment of ovarian cancers. This review aims to summarize the recent researches and clinical progress on PARP inhibitors as novel target agents in ovarian cancer.
卵巢癌是妇科癌症中死亡率最高的疾病。铂类紫杉烷化疗与根治性手术联合是其金标准。尽管在过去几十年中细胞毒性药物有了一些调整，但大多数患者仍会复发，总体生存率并未得到显著提高。耐药性的发展和疾病的复发促使人们对可用于治疗卵巢癌的其他靶点进行研究。在这些靶点中，聚腺苷二磷酸核糖聚合酶（PARP）代表了一种针对肿瘤生长中特定途径的新方法。PARP加速参与DNA修复的蛋白质的聚ADP核糖基化反应。PARP抑制剂已在具有BRCA突变、其他DNA修复基因缺陷或调节DNA修复的信号通路的癌症中显示出活性，或与不涉及DNA修复功能障碍的DNA损伤剂联合使用时显示出活性。已经开发出多种PARP抑制剂，此类药物正在临床试验中进行研究，以确定它们在卵巢癌治疗中的作用。本综述旨在总结PARP抑制剂作为卵巢癌新型靶向药物的最新研究和临床进展。
