HER2阳性的进展期胃癌目前和未来的靶向治疗  

Present and Future Targeted Therapy of HER2-positive Advanced Stomach Cancer

作　　者：余文[1] 刘宝清[1] 门斯烨[1] 薛雾松[1] 张少辉[1] 刘会良[1] 周春宇[1] 杨成城[1] 吴伟[1] 

机构地区：[1]北京中医药大学东方医院普通外科,北京100078

出　　处：《中国医药指南》2013年第21期92-95,共4页Guide of China Medicine

摘　　要：目前对胃癌中人表皮生长因子受体(2HER2)的预测价值存有争议。当前的治疗指南已经把检测胃癌中HER2状态作为标准化操作。最近,在治疗HER2阳性进展期胃癌中,曲妥珠单抗已经成为一线靶向治疗用药,而原发与继发性药物抵抗则成为主要问题,需要新的治疗策略来克服这种抵抗。许多HER2阳性进展期胃癌患者在接受曲妥珠单抗治疗后都出现疾病进展,必须接受二线方案治疗。新的靶向药物,诸如酪氨酸激酶抑制剂(TKI)拉帕替尼、哺乳动物雷帕霉素靶蛋白(mTOR)通路抑制剂依维莫司、热休克蛋白90(HSP90)抑制剂AUY922、HER二聚化抑制剂帕妥珠单抗以及抗体-药物偶联物曲妥珠单抗-emtansine(T-DM1),在以曲妥珠单抗为基础的一线治疗失败时可以成为二线治疗用药。The prognostic value of human epidermal growth factor receptor 2 （HER2） in gastric cancer is controversial. Consensus guidelines have standardized the testing of HER2 status in gastric cancer. Recently, trastuzumab has emerged as the first targeted drug to improve overall survival when combined with chemotherapy in advanced HER2-positive gastric cancer. Primary and secondary resistance to trastuzumab has become a major problem and new strategies to overcome this resistance are needed. A high percentage of advanced HER2-positive gastric cancer patients who progress on trastuzumab therapy are candidates for second-line therapy. New families of targeted drugs, including tyrosine kinase inhibitors （TKIs） such as lapatinib, mammalian target of rapamycin （roTOR） pathway inhibitors such as everolimus, heat-shock protein 90 （HSP90） inhibitors such as AUY922, HER dimerization inhibitors such as pertuzumab, and antibody-chemotherapy conjugates such as trastuzumab-emtansine （T-DM1）, could offer alternative second-line treatments when trastuzumab-based first-line therapy fails.

关 键 词：胃癌 人表皮生长因子受体 曲妥珠单抗抵抗 多靶点酪氨酸激酶抑制剂 二线治疗 靶向治疗 

分 类 号：R735.2[医药卫生—肿瘤]