潜在的BRCA变异在多种实体肿瘤患者中的不确定性角色：身体之一，众志成城？
Potential agnostic role of BRCA alterations in patients with several solid tumors: one for all, all for one?
发表日期：2023 Aug 01
作者：
Daniele Fanale, Lidia Rita Corsini, Erika Pedone, Ugo Randazzo, Alessia Fiorino, Marianna Di Piazza, Chiara Brando, Luigi Magrin, Silvia Contino, Paola Piraino, Tancredi Didier Bazan Russo, Calogero Cipolla, Antonio Russo, Viviana Bazan
来源：
BIOMEDICINE & PHARMACOTHERAPY
摘要：
同源重组(HR)途径中的胚系BRCA1/2突变被视为遗传性乳腺和卵巢癌(HBOC)的主要易感性生物标志物。现代分子生物学技术使得可以表征多种恶性肿瘤中的胚系和体细胞BRCA1/2突变，扩大了BRCA1/2突变肿瘤的范围。近年来，除了预防价值外，BRCA基因检测还具有预测和预后管理的意义。无偏性指示分子的批准正在引领一种新的临床模式，被定义为“突变型”。在这些药物中，对BRCA1/2缺陷肿瘤的Poly（ADP）-核糖聚合酶抑制剂(PARPi)已广泛研究，导致了治疗应用的增加。在本综述中，我们概述了主要临床研究，描述了BRCA突变肿瘤和PARPi反应之间的关联，并着重讨论了关于BRCA1/2突变在多种实体肿瘤中可能的无偏性指示的争议性证据。版权所有 © 2023. Elsevier B.V. 发布。
Germline BRCA1/2 alterations in the Homologous Recombination (HR) pathway are considered as main susceptibility biomarkers to Hereditary Breast and Ovarian Cancers (HBOC). The modern molecular biology technologies allowed to characterize germline and somatic BRCA1/2 alterations in several malignancies, broadening the landscape of BRCA1/2-alterated tumors. In the last years, BRCA genetic testing, beyond the preventive value, also assumed a predictive and prognostic significance for patient management. The approval of molecules with agnostic indication is leading to a new clinical model, defined "mutational". Among these drugs, the Poly (ADP)-Ribose Polymerase inhibitors (PARPi) for BRCA1/2-deficient tumors were widely studied leading to increasing therapeutic implications. In this Review we provided an overview of the main clinical studies describing the association between BRCA-mutated tumors and PARPi response, focusing on the controversial evidence about the potential agnostic indication based on BRCA1/2 alterations in several solid tumors.Copyright © 2023. Published by Elsevier B.V.