肿瘤微环境参与介导HER2阳性乳腺癌曲妥珠单抗耐药的研究进展  

Research progress on the involvement of tumor microenvironment in mediating trastuzumab resistance in HER2-positive breast cancer

作　　者：曹长青 郭新艳 高源 张存 唐海利 樊东 杨小军 张松 赵华栋 Cao Changqing;Guo Xinyan;Gao Yuan;Zhang Cun;Tang Haili;Fan Dong;Yang Xiaojun;Zhang Song;Zhao Huadong(Department of general surgery,The Second Affiliated Hospital of Air Force Medical University,Xi’an Shaanxi Province 710032,China;Department of pharmacy,The Air Force Medical University,Xi’an Shaanxi Province 710032,China;Pharmacy Department of the Second Affiliated Hospital of Air Force Military Medical University,Xi’an Shaanxi Province 710032,China)

机构地区：[1]空军军医大学附属第二医院普外科,陕西西安710032 [2]空军军医大学肿瘤生物学国家重点实验室,生物制药学教研室,陕西西安710032 [3]空军军医大学附属第二医院药剂科,陕西西安710032

出　　处：《中华普外科手术学杂志（电子版）》2024年第1期90-95,共6页Chinese Journal of Operative Procedures of General Surgery(Electronic Edition)

基　　金：国家自然科学基金(81902678);陕西省重点研发计划一般项(2021SF-223)。

摘　　要：曲妥珠单抗是一种靶向人表皮生长因子受体-2(HER2)的单克隆抗体,具有调控HER2的表达与其下游信号功能、调控细胞周期、抑制酪氨酸激酶活性、减缓肿瘤血管生成和调节肿瘤免疫微环境的作用。在HER2阳性乳腺癌中,曲妥珠单抗作为一线治疗药物贯穿术前新辅助治疗和术后靶向治疗,然而近年来随着乳腺癌成为女性第一高发肿瘤,曲妥珠单抗的耐药问题越来越普遍。研究表明,肿瘤微环境在曲妥珠单抗的耐药问题中发挥重要作用,可以影响HER2阳性乳腺癌的发展及预后。这篇综述总结了近些年肿瘤微环境在曲妥珠单抗耐药机制方面的进展,重点强调了NK细胞的作用,并对克服耐药性,改善患者预后的方法进行了概述。Trastuzumab is a monoclonal antibody targeting human epidermal growth factor receptor-2(HER2),which can regulate the expression of HER2 and its downstream signaling function,regulate cell cycle,inhibit tyrosine kinase activity,slow down tumor angiogenesis and regulate tumor immune microenvironment.In HER2-positive breast cancer,trastuzumab is used as a first-line treatment throughout preoperative neoadjuvant therapy and postoperative targeted therapy.However,in recent years,as breast cancer has become the first most frequent tumor in women,the problem of trastuzumab resistance has become more and more common.Studies have shown that tumor microenvironment plays an important role in trastuzumab resistance,which can affect the development and prognosis of HER2-positive breast cancer.This review summarizes the progress of tumor microenvironment in the mechanism of trastuzumab resistance in recent years,emphasizes the role of NK cells,and Outlines the methods to overcome resistance and improve patient prognosis.

关 键 词：人表皮生长因子受体-2 曲妥珠单抗 耐药 肿瘤微环境 ADCC效应 

分 类 号：R737.9[医药卫生—肿瘤]