Wang Lizhe, Wang Yu, Li Yueyang, Zhou Li, Du Jiahui, Wang Jin, Liu SiHan, Cao Yongyi, Li Yuzhi, Yang Wenying, Zhu Ting
The Third Affiliated Hospital of Anhui Medical University, Hefei first people's Hospital, Hefei, China.
Front Oncol. 2024 Nov 25;14:1389390. doi: 10.3389/fonc.2024.1389390. eCollection 2024.
Breast cancer that overexpresses Human Epidermal Growth Factor Receptor 2 (HER2+) due to gene amplification or overexpression constitutes 15-20% of all breast cancer cases. Trastuzumab, the first FDA-approved monoclonal antibody targeting HER2, serves as the standard first-line treatment for HER2-positive advanced breast cancer, as recommended by multiple clinical guidelines.Currently, accumulated clinical evidence reveals a considerable degree of variability in the response of HER2+ breast cancer to trastuzumab treatment. Specifically, over 50% of patients either do not respond to or develop resistance against trastuzumab.The specific mechanisms of resistance to trastuzumab are currently unclear. This paper aims to review the existing research on the resistance mechanisms of trastuzumab, based on its target, from aspects such as genetic loci, molecular structure, signaling pathways, and the tumor microenvironment and to outline current research progress and new strategies.
由于基因扩增或过表达而过度表达人表皮生长因子受体2（HER2+）的乳腺癌占所有乳腺癌病例的15%-20%。曲妥珠单抗是首个获美国食品药品监督管理局（FDA）批准的靶向HER2的单克隆抗体，正如多项临床指南所推荐的那样，它是HER2阳性晚期乳腺癌的标准一线治疗药物。目前，积累的临床证据显示，HER2+乳腺癌对曲妥珠单抗治疗的反应存在相当大的变异性。具体而言，超过50%的患者对曲妥珠单抗无反应或产生耐药性。目前尚不清楚曲妥珠单抗耐药的具体机制。本文旨在基于曲妥珠单抗的靶点，从基因位点、分子结构、信号通路以及肿瘤微环境等方面，综述关于曲妥珠单抗耐药机制的现有研究，并概述当前的研究进展和新策略。
