曲妥珠单抗耐药机制的必威体育精装版研究进展.pdfVIP

中国癌症杂志 2010年第20卷第3期 《 》 232 CHINA ONCOLOGY 2010 Vol.20 No.3 曲妥珠单抗耐药机制的必威体育精装版研究进展 张艳 综述　张锦生 审校 复旦大学医学院病理学系，上海 200032 　　［摘要］　人类表皮生长因子受体2（human epidermal growth factor receptor 2，Her-2）在20%～25% 的侵袭性乳腺癌中有过度表达，且其过度表达与乳腺癌的侵袭性和生存率相关。曲妥珠单抗（商品名：赫赛 汀，herceptin）是一种已广泛应用于临床治疗的抗Her-2的单克隆抗体，其与化疗药物联用可以明显延长患者 的无病生存期，但Her-2表达阳性的乳腺癌细胞易对曲妥珠单抗产生耐药性。本文系统总结了曲妥珠单抗的耐 药机制及相关必威体育精装版研究进展，包括PI3K/AKT信号通路过度激活、表皮生长因子受体家族（epidermal growth  factor receptor family，EGFR family）及其配体的异常表达、Her-2或曲妥珠单抗封闭、胰岛素样生长因子 1受体（insulin-like growth factor 1 receptor，IGF-1R）旁路活化PI3K/AKT通路、Darpp-32和t-Darpp过 度表达、肿瘤细胞自体吞噬、热休克蛋白27（heat shock protein 27，HSP27）过度表达等。 　　 ［关键词］　人表皮生长因子受体2；　曲妥珠单抗；　PI3K/AKT；　Darpp-32；　t-Darpp；　 自体吞噬；　HSP27 　　中图分类号：R730.53　　文献标识码：A　　文章编号：1007-3639(2010)03-0232-05 An updated review of the research on Her-2-targeted antibody resistance mechanisms　 ZHANG Yan,ZHANG Jin-sheng (Department of Pathology,Shanghai Medical College,Fudan  University,Shanghai 200032,China) Correspondence to：ZHANG Jin-sheng　E-mail：jszhang44@shmu.edu.cn 　　［Abstract ］ Human epidermal growth factor receptor 2 (Her-2), which is often over-expressed in 20%-25% of invasive breast cancer patients, is associated with an aggressive tumor phenotype and therefore, a reduced survival rate. As a widely clinically applied Her-2-targeted monoclonal antibody, herceptin, when combined with chemotherapy, significantly increases the survival time of patients without tumors. However, the majority of the cancers that initially respond positively to herceptin begin to counteract against the treatment within just 1 year. This study described several