Clinical Research Center, Women's Hospital School of Medicine Zhejiang University, Hangzhou, China.
Department of Gynecology Oncology, Harbin Medical University Cancer Hospital, Harbin, China.
Front Immunol. 2021 Oct 12;12:661115. doi: 10.3389/fimmu.2021.661115. eCollection 2021.
Immune checkpoint inhibitors (ICI) have emerged as a powerful oncologic treatment modality for patients with different solid tumors. Unfortunately, the efficacy of ICI monotherapy in ovarian cancer is limited, and combination therapy provides a new opportunity for immunotherapy in ovarian cancer. DNA damage repair (DDR) pathways play central roles in the maintenance of genomic integrity and promote the progression of cancer. A deficiency in DDR genes can cause different degrees of DNA damage that enhance local antigen release, resulting in systemic antitumor immune responses. Thus, the combination of DDR inhibitors with ICI represents an attractive therapeutic strategy with the potential to improve the clinical outcomes of patients with ovarian cancer. In this review, we provide an overview of the interconnectivity between DDR pathway deficiency and immune response, summarize available clinical trials on the combination therapy in ovarian cancer, and discuss the potential predictive biomarkers that can be utilized to guide the use of combination therapy.
免疫检查点抑制剂(ICI)已成为治疗不同实体瘤患者的一种强大的肿瘤治疗方法。不幸的是,ICI 单药治疗在卵巢癌中的疗效有限,联合治疗为卵巢癌的免疫治疗提供了新的机会。DNA 损伤修复(DDR)途径在维持基因组完整性方面发挥着核心作用,并促进癌症的进展。DDR 基因的缺陷会导致不同程度的 DNA 损伤,增强局部抗原的释放,从而引发全身性抗肿瘤免疫反应。因此,DDR 抑制剂与 ICI 的联合应用代表了一种有吸引力的治疗策略,有可能改善卵巢癌患者的临床结局。在这篇综述中,我们概述了 DDR 途径缺陷与免疫反应之间的相互关系,总结了卵巢癌中联合治疗的现有临床试验,并讨论了可用于指导联合治疗应用的潜在预测生物标志物。