PARP抑制剂在卵巢癌中的研究进展

Research progress of PARP inhibitors in ovarian cancer

卵巢癌是死亡率最高的妇科恶性肿瘤之一。传统的化疗药物不能提高卵巢的生存率。近年来,聚腺苷二磷酸核糖聚合酶[poly（ADP—ribose）polymerase,PARP]抑制剂在乳腺癌易感基因（breast cancer susceptibility gene,BRCA）突变的卵巢癌患者中可以明显改善无瘤生存期,可能改变这部分卵巢癌患者的生存预后。聚腺苷二磷酸核糖聚合酶[poly（ADP—ribose）polymerase,PARP]抑制剂通过抑制肿瘤细胞DNA损伤修复,造成DNA损伤累积,最终杀死肿瘤细胞。在乳腺癌易感基因1（breast cancer susceptibility gene,BRCA）/BRCA2突变的卵巢癌患者中,PARP抑制剂和BRCA突变产生的合成致死效应为抗癌药物的研发提供了新的方向。目前已研发出许多选择性和敏感性均较好的PARP抑制剂,且大部分己进入临床试验阶段。虽然PARP抑制剂单药在BRCA突变的卵巢癌患者中可产生治疗效果,但临床应用时,仍与其他化疗药物或放射治疗联合使用。本文对近年来开展的PARP抑制剂的临床试验予以介绍,对PARP抑制剂的机制、应用及研究进展等方面作一综述。

Ovarian cancer is one of the highest mortality rate of gynecologic malignant tumors. Chemotherapy can improve the survival rate of the traditional ovary. In recent years, PARP [poly（ADP-ribose）polymerase]inMbitors in breast cancer susceptibility gene （breast cancer susceptibility gene, BRCA） mutations in patients with ovarian cancer can significantly improve the disease-free survival, may change the prognosis of patients with ovarian cancer. This part of PARP [poly（ADP-ribose）polymerase] inhibitors, inhibiting the repairment of DNA damage in tumor cell, causing DNA damage accumulation, eventually killing tumor cells.In breast cancer susceptibility gene 1 （breast cancer susceptibility genel, BRCA1）/BRCA2 mutation patients with ovarian cancer, PARP inhibitors and BRCA mutation of the synthetic lethal effect provides a new direction for the development of anti-cancer drugs. Now, many highly selective and sensitive PARP inhibitors have been developed and applied in clinical trials.Although PARP inhibitor monotherapy can produce a therapeutic effect in BRCA mutation in patients with ovarian cancer, but the clinical application is still used in combination with other chemotherapy or radiotherapy. This review is focused on the recent progress in clinical trials of PARP inhibitors in combination with common chemotherapeutic agents.