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Open Access Article

International Journal of Clinical Research. 2022; 6: (2) ; 19-24 ; DOI: 10.12208/j.ijcr.20220048.

Advances on Resistance Mechanisms of Trastuzumab
曲妥珠单抗耐药机制研究进展

作者: 邢一舒, 王赛琪, 吕慧芳, 聂彩云, 王建正, 赵慧晨, 陈小兵 *

郑州大学附属肿瘤医院,河南省肿瘤医院消化内科 河南郑州

*通讯作者: 陈小兵,单位:郑州大学附属肿瘤医院,河南省肿瘤医院消化内科 河南郑州;

发布时间: 2022-04-24 总浏览量: 624

摘要

曲妥珠单抗是首个靶向人类表皮生长因子受体-2(Human Epidermal Growth Factor Receptor 2,HER2)的人源化单克隆抗体药物,极大地改善了HER2阳性乳腺癌与胃癌患者的治疗效果及预后,成为HER2阳性晚期乳腺癌与胃癌一线治疗策略。然而,多数患者在使用曲妥珠单抗治疗一年后发生继发耐药,导致疾病进展。研究表明,HER2蛋白结构改变、其他人类表皮生长因子受体(Human Epidermal Growth Factor Receptor,HER)家族受体及其配体信号通路激活、下游磷脂酰肌醇-3激酶(phosphoinositide-3-kinase,PI3K)信号通路改变、上皮间质转化(epithelial-mesenchymal transition,EMT)发生以及抗体依赖的细胞介导的细胞毒作用 (antibody-dependent cell-mediated cytotoxicity,ADCC)等多种机制参与了曲妥珠单抗耐药,本文就曲妥珠单抗耐药机制进行综述,为曲妥珠单抗的治疗提供预测生物标志物、克服耐药的方法,进行更加有效的靶向用药或者联合治疗从而改善患者预后。

关键词: 曲妥珠单抗耐药;HER2;PI3K信号通路;EMT;ADCC

Abstract

Trastuzumab, thefirstmonoclonal antibody targeting Human Epidermal Growth Factor Receptor 2 (HER2) hasimprovedthetreatment effect andprognosis of patients with HER2-positive breast cancer and gastric cancer. Trastuzumab has already been the first-line treatment medicine in aforementioned advanced cancers. However, most patients develop acquired resistance after 1 year, resulting in the disease progression. Researches indicate that there are multiple mechanisms mediating trastuzumab resistance such as the change of HER2 protein structure, activation of signaling pathways among other members of HER Family and their ligands, changes of downstream PI3K signaling pathway, epithelial-mesenchymal transition, antibody-dependent cell-mediated cytotoxicity(ADCC) and so on. In this review, we summarize the mechanisms of trastuzumab resistance, in order to provide predictive biomarkers and overcome resistance of trastuzumab therapy. Furthermore, we hope to find more effective targeted drugs or combination therapies.

Key words: Trastuzumab Resistance; HER2; PI3K; EMT; ADCC

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引用本文

邢一舒, 王赛琪, 吕慧芳, 聂彩云, 王建正, 赵慧晨, 陈小兵, 曲妥珠单抗耐药机制研究进展[J]. 国际临床研究杂志, 2022; 6: (2) : 19-24.