聚ADP核糖聚合酶-1及其抑制剂在肿瘤细胞中的研究进展.pdfVIP

1612 中国肿瘤临床 2011 年第38 卷第24 期 聚ADP核糖聚合酶-1及其抑制剂在肿瘤细胞中的 研究进展 ①② ② 周 强 综述 卢 铀 审校 摘要 聚ADP 核糖聚合酶-1（PARP- 1）在DNA 单链断裂的碱基切除修复中具有非常重要的作用，在人类多种肿瘤中过度表 达且过度表达者预后较差。利用合成致死原理，对于因BRCA1或BRCA2 基因突变而同源重组修复DNA 双链断裂缺陷的肿瘤细 胞，抑制其PARP- 1 活性将导致肿瘤细胞死亡。PARP 抑制剂对于携带BRCA 基因突变肿瘤患者具有一定的治疗作用，其临床应 用价值已在多项临床试验中得到了证实。PARP- 1 可能会成为肿瘤治疗的重要靶点。 关键词 聚ADP 核糖聚合酶类 聚ADP 核糖聚合酶类抑制剂 肿瘤 doi:10.3969/j.issn. 1000-8179.2011.24.035 Progress in the Research of Poly ( ADP-ribose ) Polymerase-1 and Its Inhibitors in Malignant Tumors Qiang ZHOU1,2 , You LU2 Correspondence to: You LU, E-mail: radyoulu@ 1Department of Oncology Suining Central Hospital, Suining 629000, China 2Department of Thoracic Cancer, West China Hospital of Sichuan University, Chengdu 610041, China Abstract Poly ( ADP-ribose ) polymerase- 1 ( PARP-1 ) has a vital role in base excision repair of single-strand DNA breakage, and its over-expression has often been observed in various human tumor types, which correlates with a poor outcome. PARP-1 inhibi- tion has been exploited in the repair of double-strange DNA breakage through a synthetic lethal approach for killing tumor cells with de- fects. This process is done via homologous recombination, particularly in the context of BRCA1 or BRCA2 mutation. Many clinical tri- als have demonstrated the clinical application value of PARP inhibitors in the treatment of cancer with BRCA mutations. PARP-1 will be an important target of tumor therapy. Keywords Poly ( ADP-ribose ) polymerase; Poly ( ADP-ribose ) polymerase inhibitor; Neoplasm 聚ADP 核糖聚合酶-1 ［poly （ADP-ribose ）poly⁃ （single strand breaks ，SSBs）、DNA 双链断裂（double ［1］ merase-1，PARP- 1］是PARP 超家族中结构最典型、 st