胃腸間質(zhì)瘤是胃腸道發(fā)生頻率最高的間質(zhì)來(lái)源的惡性腫瘤，徹底手術(shù)切除是其獲得根治的唯一方法，但術(shù)后復(fù)發(fā)和轉(zhuǎn)移的頻率較高。伊馬替尼在2002年被美國(guó)食品藥品管理局（FDA）批準(zhǔn)用于胃腸間質(zhì)瘤的治療，但治療失敗的病例依然不可避免。原發(fā)耐藥和繼發(fā)耐藥是伊馬替尼治療胃腸間質(zhì)瘤失敗的主要耐藥機(jī)制。相關(guān)指南推薦已獲批準(zhǔn)的用于伊馬替尼治療失敗后的酪氨酸激酶抑制劑舒尼替尼和瑞戈非尼作為二、三線藥物治療，同時(shí)ATP類似物索拉非尼、尼洛替尼、帕唑帕尼、帕納替尼和馬賽替尼，其他TKI藥物，如達(dá)沙替尼、瓦塔拉尼、莫特塞尼，以及其他靶向治療藥物依維莫司和ganetespib在臨床試驗(yàn)中顯示出對(duì)伊馬替尼耐藥胃腸間質(zhì)瘤有效。綜述伊馬替尼治療失敗后用于臨床治療胃腸間質(zhì)瘤的治療藥物的作用機(jī)制、臨床應(yīng)用、作用特點(diǎn)和主要副作用，為臨床胃腸間質(zhì)瘤的治療藥物選擇提供參考。

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.

國(guó)家自然科學(xué)基金青年科學(xué)基金項(xiàng)目（81101870）