胃肠间质瘤是胃肠道发生频率最高的间质来源的恶性肿瘤，彻底手术切除是其获得根治的唯一方法，但术后复发和转移的频率较高。伊马替尼在2002年被美国食品药品管理局（FDA）批准用于胃肠间质瘤的治疗，但治疗失败的病例依然不可避免。原发耐药和继发耐药是伊马替尼治疗胃肠间质瘤失败的主要耐药机制。相关指南推荐已获批准的用于伊马替尼治疗失败后的酪氨酸激酶抑制剂舒尼替尼和瑞戈非尼作为二、三线药物治疗，同时ATP类似物索拉非尼、尼洛替尼、帕唑帕尼、帕纳替尼和马赛替尼，其他TKI药物，如达沙替尼、瓦塔拉尼、莫特塞尼，以及其他靶向治疗药物依维莫司和ganetespib在临床试验中显示出对伊马替尼耐药胃肠间质瘤有效。综述伊马替尼治疗失败后用于临床治疗胃肠间质瘤的治疗药物的作用机制、临床应用、作用特点和主要副作用，为临床胃肠间质瘤的治疗药物选择提供参考。

Gastrointestinal stromal tumor is the most common mesenchymal tumor of the gastrointestinal tract. Surgical resection is the mainly treatment for gastrointestinal stromal tumor, but metastasis and recurrence are frequent. Imatinib was approved by FDA for the treatment of gastrointestinal stromal tumors in 2002. Treatment failure from resistance to imatinib is unavoidable for its primary and secondary drug resistance. Sunitinib and regorafenib are approved as second-and third-line agents for imatinib-resistant gastrointestinal stromal tumor. ATP mimetics, such as sorafenib, nilotinib, pazopanib, ponatinib, and masitinib provide clinical benefit in clinical trials for imatinib-resistant gastrointestinal stromal tumor. In addition, some other TKI agents such as dasatinib, vatalanib, and motesanib, and targeted therapeutic agents everolimus and ganetespib are effective. This article reviewed mechanism of action, clinical application, function, and main side effects of drugs for imatinib-resistant gastrointestinal stromal tumor to provide reference for drug selection on clinics of gastrointestinal stromal tumors.

国家自然科学基金青年科学基金项目（81101870）