Congregado Belén, Rivero Inés, Osmán Ignacio, Sáez Carmen, Medina López Rafael
Urology and Nephrology Department, University Hospital Virgen del Rocío, 41013 Seville, Spain.
Department of Pathology, Biomedical Institute of Seville (IBIS), 41013 Seville, Spain.
Biomedicines. 2022 Jun 15;10(6):1416. doi: 10.3390/biomedicines10061416.
The introduction of PARP inhibitors (PARPi) in prostate cancer is a milestone and provides a pathway to hope in fighting this disease. It is the first time that drugs, based on the concept of synthetic lethality, have been approved for prostate cancer. In addition, it is also the first time that genetic mutation tests have been included in the therapeutic algorithm of this disease, representing a significant step forward for precision and personalized treatment of prostate cancer. The objectives of this review are: (1) understanding the mechanism of action of PARPi in monotherapy and combinations; (2) gaining insights on patient selection for PARPi; (3) exposing the pivotal studies that have allowed its approval, and; (4) offering an overview of the ongoing trials. Nevertheless, many unsolved questions remain, such as the number of patients who could potentially benefit from PARPi, whether to use PARPi in monotherapy or in combination, and when is the best time to use them in advanced or localized disease. To answer these and other questions, many clinical trials are underway. Some of them have recently demonstrated promising results that may favor the introduction of new combinations in metastatic castration-resistant prostate cancer.
聚(ADP-核糖)聚合酶抑制剂(PARPi)引入前列腺癌治疗领域是一个里程碑,为抗击这种疾病带来了希望。这是基于合成致死概念的药物首次获批用于前列腺癌治疗。此外,这也是基因检测首次被纳入该疾病的治疗方案中,代表着前列腺癌精准和个性化治疗向前迈出了重要一步。本综述的目的是:(1)了解PARPi单药治疗及联合治疗的作用机制;(2)深入了解PARPi治疗的患者选择;(3)介绍使其获批的关键研究;(4)概述正在进行的试验。然而,仍有许多未解决的问题,例如可能从PARPi治疗中获益的患者数量、PARPi应单药使用还是联合使用,以及在晚期或局限性疾病中何时使用PARPi效果最佳。为回答这些及其他问题,许多临床试验正在进行。其中一些试验最近已显示出有前景的结果,这可能有利于在转移性去势抵抗性前列腺癌中引入新的联合治疗方案。