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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。
Poly (ADP-ribose) polymerase (PARP) is a very important new target in the treatment of cancer, and single-stranded DNA is repaired by base excision and repair. In recent years, new PARP inhibitors in combination with radiotherapy or chemotherapy have entered Phase I, II or III clinical trials. Numerous experimental data indicate that PARP inhibitors not only act as sensitizers for chemotherapy and radiotherapy, but also can be used alone in breast cancers with BRCA1 and BRCA2 mutations to selectively kill DNA repair deficient cancer cells. This review summarizes the mechanism of action of PARP inhibitors and clinical research results, assesses their adverse reactions and potential efficacy, and proposes possible problems in clinical strategies and future directions for their development.