Tisseverasinghe Steven, Bahoric Boris, Anidjar Maurice, Probst Stephan, Niazi Tamim
Department of Radiation Oncology, McGill University, Gatineau, QC J8V 3R2, Canada.
Department of Radiation Oncology, McGill University, Montreal, QC H3A 0G4, Canada.
Cancers (Basel). 2023 Mar 20;15(6):1849. doi: 10.3390/cancers15061849.
Poly-adenosine diphosphate-ribose polymerase plays an essential role in cell function by regulating apoptosis, genomic stability and DNA repair. PARPi is a promising drug class that has gained significant traction in the last decade with good outcomes in different cancers. Several trials have sought to test its effectiveness in metastatic castration resistant prostate cancer (mCRPC). We conducted a comprehensive literature review to evaluate the current role of PARPi in this setting. To this effect, we conducted queries in the PubMed, Embase and Cochrane databases. We reviewed and compared all major contemporary publications on the topic. In particular, recent phase II and III studies have also demonstrated the benefits of olaparib, rucaparib, niraparib, talazoparib in CRPC. Drug effectiveness has been assessed through radiological progression or overall response. Given the notion of synthetic lethality and potential synergy with other oncological therapies, several trials are looking to integrate PARPi in combined therapies. There remains ongoing controversy on the need for genetic screening prior to treatment initiation as well as the optimal patient population, which would benefit most from PARPi. PARPi is an important asset in the oncological arsenal for mCRPC. New combinations with PARPi may improve outcomes in earlier phases of prostate cancer.
聚腺苷二磷酸核糖聚合酶通过调节细胞凋亡、基因组稳定性和DNA修复在细胞功能中发挥重要作用。PARPi是一类有前景的药物,在过去十年中获得了显著关注,在不同癌症中取得了良好疗效。多项试验试图测试其在转移性去势抵抗性前列腺癌(mCRPC)中的有效性。我们进行了一项全面的文献综述,以评估PARPi在这种情况下的当前作用。为此,我们在PubMed、Embase和Cochrane数据库中进行了检索。我们回顾并比较了该主题的所有主要当代出版物。特别是,最近的II期和III期研究也证明了奥拉帕利、鲁卡帕利、尼拉帕利、他拉唑帕利在CRPC中的益处。药物有效性已通过影像学进展或总体反应进行评估。鉴于合成致死的概念以及与其他肿瘤治疗的潜在协同作用,多项试验正在寻求将PARPi纳入联合治疗。在开始治疗前是否需要进行基因筛查以及最能从PARPi中获益的最佳患者群体方面,仍存在争议。PARPi是mCRPC肿瘤治疗武器库中的一项重要资产。与PARPi的新联合治疗可能会改善前列腺癌早期阶段的治疗效果。