DNA损伤应答通路抑制剂治疗卵巢癌的研究进展

Research Progress of DNA Damage Response Pathway Inhibitors in the Treatment of Ovarian Cancer

卵巢癌是世界范围内发病率第二、致死率第一的妇科恶性肿瘤,约70%的病例在确诊时已被诊断为晚期且预后不良。卵巢癌的标准治疗方案是手术联合化疗,目前针对不同分子靶标和途径的多种新药正在研发中。DNA损伤应答(DNA damage response,DDR)通过修复DNA损伤起到维持基因组完整性的关键作用,被视作肿瘤治疗耐药性的关键。与正常细胞相比,癌细胞通常具有DDR缺陷和DNA损伤修复障碍,因而利用癌细胞特有的DDR缺陷设计出特异性抑制剂为卵巢癌的靶向治疗提供了新的方向。综述DDR途径中5种激酶抑制剂的作用机制及其治疗卵巢癌的研究进展,以期为卵巢癌的治疗提供新思路。

Ovarian cancer is a cancer with second highest morbidity and highest fatality of all gynecological malignant tumors all over the world.About 70%of the cases were diagnosed with advanced stage and the prognosis of them was poor.Surgery combined with chemotherapy is the standard treatment for ovarian cancer and lots of new drugs targeting different kinds of molecular pathways are under developing now.DNA damage response(DDR)plays a key role in maintaining genomic integrity by repairing DNA damage,and is regarded as a key to tumor drug resistance.Compared with normal cells,cancer cells usually have DDR defects and DNA damage repair disorder.Therefore,designing specific inhibitors targeting specific DDR defects in cancer cells provides a new direction for the treatment of ovarian cancer.This article reviews the mechanism and research progress of five kinase inhibitors of DDR pathway to identify a new way for the therapy of ovarian cancer.