PDF(Pubmed)
Abstract：
About 50% of High Grade Serous Ovarian Cancer exhibit a high degree of genomic instability due to mutation of genes involved in Homologous Recombination (HRD) and such defect accounts for synthetic lethality mechanism of PARP inhibitors (PARP-i). Several clinical trials have shown how BRCA and HRD mutational status profoundly affect first line chemotherapy as well as response to maintenance therapy with PARP-i, hence Progression Free Survival and Overall Survival. Consequently, there is urgent need for the development of increasingly reliable HRD tests, overcoming present limitations, as they play a key role in the diagnostic and therapeutic process as well as have a prognostic and predictive value. In this review we offer an overview of the state of the art regarding the actual knowledge about BRCA and HRD mutational status, the rationale of PARPi use and HRD testing (current and in development assays) and their implications in clinical practice and in the treatment decision process, in order to optimize and choose the best tailored therapy in patients with ovarian cancer.
摘要：
约50%的高级别浆液性卵巢癌由于参与同源重组(HRD)的基因的突变而表现出高度的基因组不稳定性,并且此类缺陷解释了PARP抑制剂(PARP-i)的合成致死机制。一些临床试验表明，BRCA和HRD突变状态如何深刻影响一线化疗以及对PARP-i维持治疗的反应。因此无进展生存率和总生存率。因此,迫切需要开发越来越可靠的人力资源开发测试，克服目前的局限性，因为它们在诊断和治疗过程中起着关键作用，并且具有预后和预测价值。在这篇综述中，我们提供了关于BRCA和HRD突变状态的实际知识的最新水平的概述，PARPi使用和HRD测试（当前和开发中的测定）的基本原理及其在临床实践和治疗决策过程中的意义，以优化和选择适合卵巢癌患者的最佳治疗方案。
