Curr Opin Oncol. 2019 Sep;31(5):394-403. doi: 10.1097/CCO.0000000000000557.
In the past few years, the advent of PARP inhibitors has been a revolution in the management of ovarian cancer. Patients harboring somatic or germ line BRCA1/2 mutations exhibit different clinical and treatment response behavior. The BRCA gene is involved in repairing DNA repair via homologous recombination, and mutation of this gene leads to homologous recombination deficiency (HRD).
HRD constitutes a therapeutic opportunity for these patients, thanks to the development of poly(ADP-ribose) polymerase inhibitors (PARPi) in the late 2000s. Indeed, using PARPi in patients with HRD simultaneously compromises two mechanisms of DNA repair, resulting in synthetic lethality.
This breakthrough in clinical practice has raised remaining questions: which population will most benefit from PARPi? Are all ovarian cancers susceptible to synthetic lethal strategy? At which stage of ovarian cancer should PARPi be used? Is earlier always better? Are PARPi all equivalent? Which strategies are reasonable to overcome PARPi resistance? Which combination strategies should be efficient?
在过去的几年中，聚腺苷二磷酸核糖聚合酶（PARP）抑制剂的出现彻底改变了卵巢癌的治疗模式。携带体细胞或种系 BRCA1/2 突变的患者表现出不同的临床和治疗反应特征。BRCA 基因参与同源重组修复 DNA，该基因的突变会导致同源重组缺陷（HRD）。
由于 21 世纪 10 年代后期聚（ADP-核糖）聚合酶抑制剂（PARPi）的开发，HRD 为这些患者提供了治疗机会。事实上，在 HRD 患者中使用 PARPi 同时破坏了两种 DNA 修复机制，导致合成致死。
这一临床实践的突破提出了一些尚未解决的问题：哪些人群将从 PARPi 中获益最大？所有卵巢癌都容易受到合成致死策略的影响吗？PARPi 应该在卵巢癌的哪个阶段使用？早期治疗是否总是更好？PARPi 是否都等效？有哪些合理的策略可以克服 PARPi 耐药性？哪些联合策略会更有效？
