CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：Recent Insights into PARP and Immuno-Checkpoint Inhibitors in Epithelial Ovarian Cancer.
Recent Insights into PARP and Immuno-Checkpoint Inhibitors in Epithelial Ovarian Cancer.
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卵巢癌是最常见的妇科癌症之一，在女性生殖系统癌症中死亡率最高。上皮性卵巢癌（EOC）约占所有卵巢恶性肿瘤的90%。标准治疗策略包括细胞减灭术，并辅以术前或术后以铂类为基础的化疗。
然而，高达80%的患者在完成治疗后12-18个月内复发，随后根据铂敏感性接受一线化疗。BRCA1/2基因突变是EOC中最重要的分子异常，可作为预后和预测生物标志物。聚ADP核糖聚合酶（PARP）抑制剂通过合成致死利用DNA修复通路的缺陷。它们还被证明可将PARP1和PARP2捕获在DNA上，导致PARP-DNA复合物的形成。奥拉帕利、芦卡帕利和尼拉帕利均已获得美国食品药品监督管理局（FDA）和/或欧洲药品管理局（EMA）批准，用于不同情况下EOC的治疗。免疫检查点抑制剂（ICI）已改善多种癌症的生存，目前正在EOC中进行评估。
然而，尽管免疫治疗在其他恶性肿瘤中取得了成功，抑制免疫检查点程序性细胞死亡（PD-1）或其配体（PD-L1）的抗体在EOC中迄今仅取得有限结果，中位缓解率最高为10%。
因此，ICI尚未获批用于EOC的治疗。本文对合成致死PARP抑制剂的最新进展及其耐药机制进行了全面深入的探讨。我们还总结了关于免疫检查点抑制剂作用、疫苗治疗以及过继性免疫治疗在治疗上皮性卵巢癌中的数据。
Ovarian cancer is one of the most common gynecologic cancers and has the highest mortality rate of any other cancer of the female reproductive system. Epithelial ovarian cancer (EOC) accounts for approximately 90% of all ovarian malignancies. The standard therapeutic strategy includes cytoreductive surgery accompanied by pre- or postoperative platinum-based chemotherapy. Nevertheless, up to 80% of the patients relapse within the following 12-18 months from the completion of the treatment and then receive first-line chemotherapy depending on platinum sensitivity.
Mutations in BRCA1/2 genes are the most significant molecular aberrations in EOC and serve as prognostic and predictive biomarkers. Poly ADP-ribose polymerase (PARP) inhibitors exploit defects in the DNA repair pathway through synthetic lethality. They have also been shown to trap PARP1 and PARP2 on DNA, leading to PARP-DNA complexes.
Olaparib, rucaparib, and niraparib have all obtained Food and Drug Administration (FDA) and/or the European Medicine Agency (EMA) approval for the treatment of EOC in different settings. Immune checkpoint inhibitors (ICI) have improved the survival of several cancers and are under evaluation in EOC.
However, despite the success of immunotherapy in other malignancies, the use of antibodies inhibiting the immune checkpoint programmed cell death (PD-1) or its ligand (PD-L1) obtained modest results in EOC so far, with median response rates of up to 10%. As such, ICI have not yet been approved for the treatment of EOC.
We herein provided a comprehensive insight into the most recent progress in synthetic lethality PARP inhibitors, along with the mechanisms of resistance.
We also summarised data regarding the role of immune checkpoint inhibitors, the use of vaccination therapy, and adoptive immunotherapy in treating epithelial ovarian cancer.
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