Chiang Ying-Cheng, Lin Po-Han, Cheng Wen-Fang
Department of Obstetrics and Gynecology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan.
Front Oncol. 2021 Oct 14;11:675972. doi: 10.3389/fonc.2021.675972. eCollection 2021.
Epithelial ovarian cancer (EOC) patients are generally diagnosed at an advanced stage, usually relapse after initial treatments, which include debulking surgery and adjuvant platinum-based chemotherapy, and eventually have poor 5-year survival of less than 50%. In recent years, promising survival benefits from maintenance therapy with poly(ADP-ribose) polymerase (PARP) inhibitor (PARPi) has changed the management of EOC in newly diagnosed and recurrent disease. Identification of mutations and/or homologous recombination deficiency (HRD) is critical for selecting patients for PARPi treatment. However, the currently available HRD assays are not perfect predictors of the clinical response to PARPis in EOC patients. In this review, we introduce the concept of synthetic lethality, the rationale of using PARPi when HRD is present in tumor cells, the clinical trials of PARPi incorporating the HRD assays for EOC, the current HRD assays, and other HRD assays in development.
上皮性卵巢癌(EOC)患者通常在晚期被诊断出来,在包括肿瘤减灭术和铂类辅助化疗在内的初始治疗后通常会复发,最终5年生存率低于50%,预后较差。近年来,聚(ADP-核糖)聚合酶(PARP)抑制剂(PARPi)维持治疗带来的显著生存获益改变了新诊断和复发性EOC的治疗策略。识别突变和/或同源重组缺陷(HRD)对于选择PARPi治疗的患者至关重要。然而,目前可用的HRD检测方法并非EOC患者对PARPi临床反应的完美预测指标。在本综述中,我们介绍了合成致死的概念、肿瘤细胞存在HRD时使用PARPi的原理、纳入HRD检测的EOC患者PARPi临床试验、当前的HRD检测方法以及其他正在开发的HRD检测方法。