Lorusso Domenica, Tripodi Elisa, Maltese Giuseppa, Lepori Stefano, Sabatucci Ilaria, Bogani Giorgio, Raspagliesi Francesco
Gynecologic Oncology Unit, Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy.
Drug Des Devel Ther. 2018 May 29;12:1501-1509. doi: 10.2147/DDDT.S124447. eCollection 2018.
Epithelial ovarian cancer is the sixth most common cancer among women worldwide and the first cause of death among gynecological malignancies. Most of the patients present recurrent disease and unfortunately cannot be cured. The unsatisfactory results obtained with salvage chemotherapy have elicited investigators to search for novel biological agents capable of achieving a better control of the disease. In the setting of homologous recombination deficiency, the DNA errors that occur cannot be accurately repaired, and the treatment with poly(ADP-ribose) polymerase (PARP) inhibition results in definitive cell death in a process called synthetic lethality. As a result of two positive clinical trials, Olaparib was approved in 2014 by U.S. Food and Drug Administration and European Medicines Agency as the first-in-class PARP inhibitor. Olaparib is effective and well tolerated in homologous recombination deficient patients. Several studies with Olaparib have been conducted in the recurrent setting either as maintenance in platinum-responsive patients or as a single agent. Ongoing trials are focused on the use of olaparib as maintenance in the first-line ovarian cancer setting alone or in combination with antiangiogenic agents. Future perspectives will probably investigate the association of olaparib with novel agents as check-point inhibitors and PI3K-AKT inhibitors. The PARP inhibitor era is just at the beginning.
上皮性卵巢癌是全球女性中第六大常见癌症,也是妇科恶性肿瘤的首要死因。大多数患者会出现疾病复发,不幸的是无法治愈。挽救性化疗取得的不尽人意的结果促使研究人员寻找能够更好控制该疾病的新型生物制剂。在同源重组缺陷的情况下,发生的DNA错误无法准确修复,使用聚(ADP - 核糖)聚合酶(PARP)抑制剂进行治疗会在一个称为合成致死的过程中导致细胞最终死亡。由于两项临床试验取得阳性结果,奥拉帕尼在2014年被美国食品药品监督管理局和欧洲药品管理局批准为首个PARP抑制剂。奥拉帕尼在同源重组缺陷患者中有效且耐受性良好。已经针对奥拉帕尼在复发情况下作为铂敏感患者的维持治疗或作为单一药物进行了多项研究。正在进行的试验集中于将奥拉帕尼单独或与抗血管生成药物联合用于一线卵巢癌的维持治疗。未来的研究可能会探讨奥拉帕尼与新型药物如检查点抑制剂和PI3K - AKT抑制剂的联合应用。PARP抑制剂时代才刚刚开始。