常晋霞,李兴妍,刘文虎.曲妥珠单抗获得性耐药机制及应对策略[J].中国肿瘤,2018,27(4):299-305.
曲妥珠单抗获得性耐药机制及应对策略
Acquired Trastuzumab Resistance:Mechanisms and Coping Strategies
投稿时间:2018-01-24  
DOI:10.11735/j.issn.1004-0242.2018.04.A010
中文关键词:  曲妥珠单抗  HER2  获得性耐药
英文关键词:rastuzumab  HER2  acquired resistance
基金项目:
作者单位
常晋霞 川北医学院基础医学院 
李兴妍 汉中市城固县食品药品检验检测中心 
刘文虎 川北医学院药学院 
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中文摘要:
      摘 要:曲妥珠单抗是靶向人表皮生长因子2(HER2)的单克隆抗体药物,对HER2表达阳性乳腺癌及胃癌治疗效果确切。然而多数患者在用药1年内出现了获得性耐药,导致其疗效降低甚至无效。研究表明,信号通路异常激活;表皮生长因子受体(EGFR)及其配体异常表达及肿瘤诱发上皮—间质转化(EMT)均可成为曲妥珠单抗耐药的重要机制,联合使用PI3K/AKT/mTOR通路抑制剂及其相关生存信号通路抑制剂可逆转曲妥珠单抗耐药。本文就曲妥珠单抗耐药机制及逆转耐药策略进行综述。
英文摘要:
      Abstract:Trastuzumab,a monoclonal antibody targeting the human epidermal factor 2(HER2),has proven to have a reliable therapeutic effect on HER2-positive breast and gastric cancer. However,the acquired resistance would occur within one year of treatment in majority of patients. As a consequence,the effect dropped even down to zero. The studies have shown that aberrant activation of signaling pathways,abnormal expression of epidermal growth factor receptor(EGFR)and its ligand,and cancer-induced epithelial-mesenchymal transition(EMT) are possibly the mechanisms of trastuzumab resistance. Therefore,combination of PI3K/AKT/mTOR pathway inhibitors and inhibitors to other relevant survival signaling pathways may reverse trastuzumab resistance. In this article,we discuss and summarize the mechanisms of trastuzumab resistance and the coping strategies.
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