Messina Carlo, Cattrini Carlo, Soldato Davide, Vallome Giacomo, Caffo Orazio, Castro Elena, Olmos David, Boccardo Francesco, Zanardi Elisa
Department of Medical Oncology, Santa Chiara Hospital, 38122 Trento, Italy.
Department of Internal Medicine and Medical Specialties (DIMI), University of Genoa, 16132 Genoa, Italy.
J Oncol. 2020 Sep 7;2020:4986365. doi: 10.1155/2020/4986365. eCollection 2020.
Despite chemotherapy and novel androgen-receptor signalling inhibitors (ARSi) have been approved during the last decades, metastatic castration-resistant prostate cancer (mCRPC) remains a lethal disease with poor clinical outcomes. Several studies found that germline or acquired DNA damage repair (DDR) defects affect a high percentage of mCRPC patients. Among DDR defects, BRCA mutations show relevant clinical implications. BRCA mutations are associated with adverse clinical features in primary tumors and with poor outcomes in patients with mCRPC. In addition, BRCA mutations predict good response to poly-ADP ribose polymerase (PARP) inhibitors, such as olaparib, rucaparib, and niraparib. However, concerns still remain on the role of extensive mutational testing in prostate cancer patients, given the implications for patients and for their progeny. The present comprehensive review attempts to provide an overview of BRCA mutations in prostate cancer, focusing on their prognostic and predictive roles.
尽管在过去几十年中化疗和新型雄激素受体信号抑制剂(ARSi)已获批准,但转移性去势抵抗性前列腺癌(mCRPC)仍然是一种致命疾病,临床结局不佳。多项研究发现,种系或获得性DNA损伤修复(DDR)缺陷影响着很大比例的mCRPC患者。在DDR缺陷中,BRCA突变具有相关的临床意义。BRCA突变与原发性肿瘤的不良临床特征以及mCRPC患者的不良结局相关。此外,BRCA突变预示着对聚ADP核糖聚合酶(PARP)抑制剂(如奥拉帕尼、卢卡帕尼和尼拉帕尼)有良好反应。然而,鉴于对患者及其后代的影响,对于在前列腺癌患者中进行广泛突变检测的作用仍存在担忧。本综述试图概述前列腺癌中的BRCA突变,重点关注其预后和预测作用。