共济失调毛细血管扩张突变和Rad3相关蛋白在卵巢癌发生发展及治疗中的应用

doi:10.12280/gjfckx.20250141

摘要/Abstract

摘要：

卵巢癌是常见的妇科恶性肿瘤，其治疗面临铂类耐药和多腺苷二磷酸核糖聚合酶抑制剂[poly (ADP-ribose) polymerase inhibitor，PARPi]耐药的双重挑战。因此，如何克服其耐药性成为研究热点。卵巢癌耐药与DNA损伤应答关键基因发生逆转突变密切相关，而共济失调毛细血管扩张突变和Rad3相关蛋白（ataxia telangiectasia mutated and Rad3-related protein，ATR）是细胞内重要的蛋白激酶，在细胞周期调控、DNA损伤修复等多个生理过程中发挥关键作用。研究发现，ATR高表达促进卵巢癌细胞的存活，增加了其对化疗药物的耐受性。综述ATR的经典生物学功能，探讨ATR在卵巢癌发生、发展中的作用，介绍以ATR为靶点的卵巢癌治疗策略，以期为卵巢癌的个体化治疗提供指导，进一步改善卵巢癌患者的预后。

关键词: DNA损伤, 卵巢肿瘤, 多（ADP核糖）聚合酶抑制剂, 抗药性, 肿瘤, 治疗, 共济失调毛细血管扩张突变和Rad3相关蛋白

Abstract:

Ovarian cancer is a common gynecological malignant tumor, and its treatment faces the dual challenge of platinum resistance and poly (ADP-ribose) polymerase inhibitor (PARPi) resistance. Therefore, how to overcome its drug resistance has become a research hotspot. The drug resistance of ovarian cancer is closely related to the reverse mutation of key genes in the DNA damage response. Ataxia telangiectasia mutated and Rad3-related protein (ATR) is an important intracellular protein kinase in cells, plays a crucial role in multiple physiological processes such as cell cycle regulation and DNA damage repair. Studies have found that high expression of ATR promotes the survival of ovarian cancer cells and increases their tolerance to chemotherapeutic drugs. This article reviews the classic biological functions of ATR, explores the role of ATR in the occurrence and development of ovarian cancer, and introduces the therapeutic strategies for ovarian cancer targeting ATR, aiming to provide guidance for the individualized treatment of ovarian cancer and further improve the prognosis of ovarian cancer patients.

Key words: DNA damage, Ovarian neoplasms, Poly(ADP-ribose) polymerase inhibitors, Drug resistance, neoplasm, Therapy, Ataxia telangiectasia mutated and Rad3-related protein

冯晓宇, 闫丽隽. 共济失调毛细血管扩张突变和Rad3相关蛋白在卵巢癌发生发展及治疗中的应用[J]. 国际妇产科学杂志, 2025, 52(3): 331-336.

FENG Xiao-yu, YAN Li-jun. The Application of Ataxia Telangiectasia Mutated and Rad3-Related Protein in the Pathogenesis, Development and Treatment of Ovarian Cancer[J]. Journal of International Obstetrics and Gynecology, 2025, 52(3): 331-336.

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