Slovak Academy of Sciences, Bratislava, Slovakia.
Neoplasma. 2010;57(5):401-5. doi: 10.4149/neo_2010_05_401.
The nuclear poly(ADP-ribose) polymerase-1 (PARP-1) represents an important novel target in cancer therapy. The enzyme is essential for single strand DNA breaks repair via base excision repair pathway. Inhibition of PARP-1 exerts "synthetic lethality" effect towards the tumors with defects in DNA repair by homologous recombination, specifically the tumors with mutations in the breast cancer associated BRCA1 and BRCA2 genes. Recent clinical data confirmed the early in vitro studies and suggest that PARP-1 inhibitors could be used not only as chemosensitizers but as well as single agents to selective kill tumors with defective DNA repair by homologous recombination. Such concept of "synthetic lethality" for tumors which have lost one DNA repair pathway by targeting a second DNA repair pathway, represents groundbreaking therapeutic strategy. The review highlights our current knowledge and ongoing clinical development/trials of PARP-1 inhibitors.
聚（ADP-核糖）聚合酶 1（PARP-1）是癌症治疗中一个重要的新型靶点。该酶对于通过碱基切除修复途径修复单链 DNA 断裂是必需的。PARP-1 的抑制作用对同源重组修复缺陷的肿瘤产生“合成致死”效应，特别是那些乳腺癌相关 BRCA1 和 BRCA2 基因突变的肿瘤。最近的临床数据证实了早期的体外研究结果，并表明 PARP-1 抑制剂不仅可以作为化疗增敏剂，而且可以作为单一药物，选择性杀死同源重组修复缺陷的肿瘤。这种通过靶向第二种 DNA 修复途径来消除一种 DNA 修复途径的肿瘤“合成致死”的概念，代表了一种开创性的治疗策略。本文综述了我们目前对 PARP-1 抑制剂的认识和正在进行的临床开发/试验。
