ATR抑制剂治疗三阴性乳腺癌的研究进展  

Recent advances on ATR inhibitors in the treatment of triple-negative breast cancer

作　　者：鞠帮辉 程方岩 姚轶群 JU Banghui;CHENG Fangyan;YAO Yiqun(Department of Breast and Thyroid Surgery,Affiliated Zhongshan Hospital of Dalian University,Dalian 116001,China)

机构地区：[1]大连大学附属中山医院乳腺甲状腺外科,辽宁大连116001

出　　处：《大连医科大学学报》2024年第6期553-558,共6页Journal of Dalian Medical University

摘　　要：三阴性乳腺癌(TNBC)是一种预后较差的乳腺癌亚型,其特征是缺乏雌激素受体(ER)、孕激素受体(PR)和人表皮生长因子受体2(HER2)。传统化疗疗效不佳,且易引起患者耐药性,导致其治疗选择非常有限。近年来,共济失调毛细血管扩张突变基因Rad3相关蛋白(ATR)作为DNA损伤应答(DDR)的关键调节因子,在TNBC治疗中显示出重要潜力。ATR抑制剂(ATRi)通过干扰DNA损伤修复,增强肿瘤细胞对DNA损伤的敏感性,尤其对共济失调毛细血管扩张突变基因蛋白(ATM)功能缺陷的TNBC细胞,可诱导合成致死效应,增强化疗和放疗的疗效。本文综述了ATRi在TNBC治疗中的作用机制、临床前研究成果及与现有治疗手段的联合应用现状,为TNBC的靶向治疗药物研发与临床治疗提供新思路。Triple-negative breast cancer(TNBC)is a subtype of breast cancer characterized by the absence of estrogen receptor(ER),progesterone receptor(PR),and human epidermal growth factor receptor 2(HER2).TNBC has limited treatment options,and its prognosis is relatively poor.Traditional chemotherapy regimens confer limited efficacy and eventually patients will develop drug resistance.Inhibitors of ataxia telangiectasia mutated Rad3-related kinase(ATRi),a key regulator of DNA damage response(DDR),has shown therapeutic potential for TNBC treatment.ATRi are capable of sensitizing tumor cells to DNA-damage by interfering with DNA repair and thereby enhancing the efficacy of chemotherapy and radiotherapy.Particularly,ATRi can induce synthetic lethality in cancer cells with ATM deficiency.This article reviews the preclinical studies applying ATRi as monotherapy or combination therapy for TNBC treatment and the related mechanisms of action,providing new insights into the future clinical trials employing ATRi-based strategies for TNBC intervention.

关 键 词：三阴性乳腺癌 ATR ATR抑制剂 DNA损伤应答 

分 类 号：R737.9[医药卫生—肿瘤]