摘要
聚腺苷二磷酸核糖聚合酶[poly(ADP-ribose)polymerase,PARP]抑制剂与乳腺癌易感基因1(breast cancer susceptibility gene 1,BRCA1)/BRCA2突变介导的合成致死理论,为抗癌药物的研发提供了新的方向。这是一种通过抑制肿瘤细胞DNA损伤修复,从而杀伤肿瘤细胞的安全而有效的新型治疗方式。自研究证实PARP抑制剂可引起乳腺癌细胞的合成致死效应以来,已研发出许多选择性和敏感性均较好的PARP抑制剂,且大部分已进入临床试验阶段。尽管PARP抑制剂单药在BRCA1/BRCA2突变的乳腺癌和卵巢癌中可发挥治疗效应,但目前的PARP抑制剂在临床应用时,仍是与其他化疗药物或放射治疗联合使用。本综述对已报道的PARP抑制剂联合常用化疗药物治疗肿瘤的研究进展进行小结。
In recent years, synthetic lethality of PARP [poly （ADP-ribose） polymerase] inhibition in cancers with BRCA1 （breast cancer susceptibility gene 1） and BRCA2 mutations appears to provide a novel, efficient and safe antitumor strategy. It was hypothesized that the mechanism underlying this new antitumor strategy was the inhibition of DNA damage repair leading to cell death. Since the synthetic lethality was confirmed in breast cancer cells by PARP inhibitor intervention, many highly selective and sensitive PARP inhibitors have been developed and applied in clinical trials. Although the effectiveness of PARP inhibitor used as a single agent can be reached in breast cancer and ovarian cancer with BRCA1 / BRCA2 mutation, it is generally advised to use PARP inhibitors in combination with chemotherapeutic agents or radiation therapy. This review is focused on the recent progress in clinical antitumor therapy with PARP inhibitors in combination with common chemotherapeutic agents.
出处
《肿瘤》
CAS
CSCD
北大核心
2013年第4期372-377,共6页
Tumor
