1] INSERM, U848, Villejuif, France [2] Institut Gustave Roussy, Villejuif, France [3] Université de Paris Sud, Villejuif, France.
1] Regina Elena National Cancer Institute, Roma, Italy [2] National Institute of Health, Rome, Italy.
Oncogene. 2014 Jul 24;33(30):3894-907. doi: 10.1038/onc.2013.352. Epub 2013 Sep 16.
Poly(ADP-ribose) polymerase (PARP) inhibitors have raised high expectations for the treatment of multiple malignancies. PARP inhibitors, which can be used as monotherapies or in combination with DNA-damaging agents, are particularly efficient against tumors with defects in DNA repair mechanisms, in particular the homologous recombination pathway, for instance due to BRCA mutations. Thus, deficient DNA repair provides a framework for the success of PARP inhibitors in medical oncology. Here, we review encouraging results obtained in recent clinical trials investigating the safety and efficacy of PARP inhibitors as anticancer agents. We discuss emerging mechanisms of regulation of homologous recombination and how inhibition of DNA repair might be used in cancer therapy. We surmise that the identification of patients that are likely to benefit from PARP inhibition will improve the clinical use of PARP inhibitors in a defined target population. Thus, we will place special emphasis on biomarker discovery.
聚（ADP-核糖）聚合酶（PARP）抑制剂为多种恶性肿瘤的治疗带来了很高的期望。PARP 抑制剂可单独使用或与 DNA 损伤药物联合使用，对 DNA 修复机制缺陷的肿瘤，特别是同源重组途径缺陷的肿瘤（例如由于 BRCA 突变）特别有效。因此，DNA 修复缺陷为 PARP 抑制剂在肿瘤学中的成功提供了框架。在这里，我们回顾了最近临床试验中获得的关于 PARP 抑制剂作为抗癌药物的安全性和有效性的令人鼓舞的结果。我们讨论了同源重组调控的新机制以及如何在癌症治疗中使用 DNA 修复抑制。我们推测，识别可能受益于 PARP 抑制的患者将改善 PARP 抑制剂在特定目标人群中的临床应用。因此，我们将特别强调生物标志物的发现。
