文章摘要

PARP抑制剂联合抗血管生成剂在卵巢癌中的相关应用

作者: 1陈洁, 1张广美
1 哈尔滨医科大学附属第一医院妇科,哈尔滨 150001
通讯: 张广美 Email: guangmeizhang@126.com
DOI: 10.3978/j.issn.2095-6959.2020.11.041
基金: 国家自然科学基金(8177101721).

摘要

多腺苷二磷酸核糖聚合酶[Poly (ADP-ribose) polymerase,PARP]抑制剂于2005年首次作为癌症靶向策略推出,是利用合成致死率的第一个临床批准的药物。它们导致晚期卵巢癌的治疗发生重大变化,并通过同源重组(homologous recombination,HR)途径改变了具有极端遗传复杂性和缺陷DNA修复的疾病的自然病史。PARP抑制剂与其他抗癌药的新型组合治疗具有挑战性,在乳腺癌易感基因(breast related cancer antigens,BRCA)突变和野生型癌症中,PARP抑制剂和生物制剂的组合均表现出良好的耐受性和临床有效性。尤其对于PARP抑制剂联合抗血管生成剂针对卵巢癌的不同作用途径,可能诱发更大的DNA损伤和HR缺乏。
关键词: 卵巢癌;乳腺癌易感基因突变;多腺苷二磷酸核糖聚合酶抑制剂;抗血管生成剂

Poly (ADP-ribose) polymerase inhibitors combined with antiangiogenic agents for the treatment of ovarian cancer

Authors: 1CHEN Jie, 1ZHANG Guangmei
1 Department of Gynecology, First Affiliated Hospital of Harbin Medical University, Harbin 150001, China

CorrespondingAuthor: ZHANG Guangmei Email: guangmeizhang@126.com

Foundation: This work was supported by the National Natural Science Foundation of China (8177101721).

Abstract

Poly (ADP-ribose) polymerase (PARP) inhibitor are the first clinically approved drugs designed to exploit the synthetic lethality rate and were first introduced as a cancer targeting strategy in 2005. They have lead to a major change in the treatment of advanced ovarian cancer and altered the natural history of diseases with extreme genetic complexity and defective DNA repair through the homologous recombination (HR) pathway. The novel combination therapies of PARP inhibitors with other anticancer drugs is challenging, and it seems that in the breast related cancer antigens (BRCA) mutation and wild type cancer, the combination of PARP inhibitor and biological agent shows good tolerance and Clinical effectiveness. In particular, different pathways of action of PARP inhibitors combined with anti-angiogenic agents against ovarian cancer may induce greater DNA damage and HR deficiency.
Keywords: ovarian cancer; breast related cancer antigens mutation; poly (ADP-ribose) polymerase inhibitors; antiangiogenic agents