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首页> 外文期刊>British Journal of Cancer >PARP inhibitors for BRCA1/2-mutated and sporadic ovarian cancer: current practice and future directions
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PARP inhibitors for BRCA1/2-mutated and sporadic ovarian cancer: current practice and future directions

机译：PPAR抑制剂对 BRCA1 / 2 突变和散发性卵巢癌的作用：当前的实践和未来的方向

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Poly(ADP-ribose) polymerase (PARP) inhibitors cause targeted tumour cell death in homologous recombination (HR)-deficient cancers, including BRCA -mutated tumours, by exploiting synthetic lethality. PARP inhibitors are being evaluated in late-stage clinical trials of ovarian cancer (OC). Recently, olaparib was the first PARP inhibitor approved in the European Union and United States for the treatment of advanced BRCA -mutated OC. This paper reviews the role of BRCA mutations for tumorigenesis and PARP inhibitor sensitivity, and summarises the clinical development of PARP inhibitors for the treatment of patients diagnosed with OC. Among the five key PARP inhibitors currently in clinical development, olaparib has undergone the most extensive clinical investigation. PARP inhibitors have demonstrated durable antitumour activity in BRCA -mutated advanced OC as a single agent in the treatment and maintenance setting, particularly in platinum-sensitive disease. PARP inhibitors are well tolerated; however, further careful assessment of moderate and late-onset toxicity is mandatory in the maintenance and adjuvant setting, respectively. PARP inhibitors are also being evaluated in combination with chemotherapeutic and novel targeted agents to potentiate antitumour activities. Current research is extending the use of PARP inhibitors beyond BRCA mutations to other sensitising molecular defects that result in HR-deficient cancer, and is defining an HR-deficiency signature. Trials are underway to determine whether such a signature will predict sensitivity to PARP inhibitors in women with sporadic OC.
机译：聚（ADP-核糖）聚合酶（PARP）抑制剂通过利用合成杀伤力，在同源重组（HR）缺陷型癌症（包括BRCA突变的肿瘤）中导致靶向肿瘤细胞死亡。 PARP抑制剂正在卵巢癌（OC）的后期临床试验中进行评估。最近，奥拉帕尼是欧盟和美国批准用于治疗晚期BRCA突变型OC的首个PARP抑制剂。本文综述了BRCA突变在肿瘤发生和PARP抑制剂敏感性方面的作用，并概述了PARP抑制剂在诊断为OC的患者中的临床发展。在目前临床开发的五种关键PARP抑制剂中，奥拉帕尼经历了最广泛的临床研究。 PARP抑制剂已在BRCA突变的晚期OC中作为单一药物在治疗和维持环境中表现出持久的抗肿瘤活性，尤其是在铂敏感疾病中。 PARP抑制剂耐受性良好;但是，在维持和辅助治疗中，分别必须进一步仔细评估中度和晚期发作毒性。还正在评估PARP抑制剂与化学治疗剂和新型靶向剂的结合以增强抗肿瘤活性。当前的研究正在将PARP抑制剂的使用范围扩展到BRCA突变以外的其他致敏分子缺陷，这些缺陷会导致HR缺乏的癌症，并且正在定义HR缺乏的特征。目前正在进行试验以确定这种特征是否可以预测散发性OC女性对PARP抑制剂的敏感性。

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