Section of Medical Oncology, Department of Surgical, Oncological and Oral Sciences, University of Palermo, 90127 Palermo, Italy.
Division of General and Oncological Surgery, Department of Surgical, Oncological and Oral Sciences, University of Palermo, 90127 Palermo, Italy.
Crit Rev Oncol Hematol. 2023 Oct;190:104086. doi: 10.1016/j.critrevonc.2023.104086. Epub 2023 Aug 2.
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.
胚系 BRCA1/2 基因在同源重组（HR）通路中的改变被认为是遗传性乳腺癌和卵巢癌（HBOC）的主要易感生物标志物。现代分子生物学技术使我们能够在多种恶性肿瘤中对胚系和体细胞 BRCA1/2 改变进行特征描述，从而拓宽了 BRCA1/2 改变肿瘤的范围。近年来，BRCA 基因检测除了具有预防价值外，还对患者管理具有预测和预后意义。具有广泛适应证的分子药物的批准正在导致一种新的临床模式，即“突变型”。在这些药物中，聚（ADP-核糖）聚合酶抑制剂（PARPi）在 BRCA1/2 缺陷型肿瘤中的广泛研究导致了更多的治疗意义。在这篇综述中，我们概述了主要的临床研究，描述了 BRCA 突变肿瘤与 PARPi 反应之间的关联，重点关注了关于基于几种实体瘤中 BRCA1/2 改变的潜在广泛适应证的有争议的证据。
