曲妥珠单抗获得性耐药机制及应对策略

Acquired Trastuzumab Resistance:Mechanisms and Coping Strategies

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/m TOR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。

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 PI3 K/AKT/m TOR 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.