聚腺苷二磷酸核糖聚合酶抑制剂的临床研究进展

聚腺苷二磷酸核糖聚合酶(PARP)在癌症治疗中是一个非常重要的新靶点,通过碱基切除修复方式对单股DNA进行修复。近年来,新的协同放疗或化疗的PARP抑制剂已经进入了I、II或III期临床试验。众多的试验数据表明PARP抑制剂不仅可以作为化疗和放疗的增敏剂,而且在BRCA1和BRCA2基因突变的乳腺癌中可单独使用,选择性杀死DNA修复缺陷的癌细胞。本文综述了PARP抑制剂的作用机制和临床研究结果,评估了其不良反应和潜在药效,并提出了临床策略中可能存在的问题以及未来发展方向。

Clinical development of poly(ADP-ribose)polymerase inhibitors

The nuclear enzyme poly(ADP-ribose)polymerase(PARP)represents an important novel target in cancer therapy.PARP is essential to the repair of single strand DNA breaks via the base excision repair pathway.Inhibitors of PARP have been in clinical trial.More recent,clinical trial data suggested that PARP inhibitors could be used not only as chemo/radiotherapy sensitizers but also as single agents to selectively kill cancers defective in DNA repair,particularly cancers with mutations in the breast cancer associated BRCA1 and BRCA2 genes.This review discussed the current clinical data with reference to activity and future directions and the possible dangers/pitfalls of this clinical strategy were explored.