中文摘要：

磷脂肌醇（PI3K）-蛋白激酶B（PKB，Akt）-雷帕霉素靶体蛋白（roTOR）通路抑制剂耐药现象的出现，与其上下游相关联的其他癌蛋白信号通路的反馈机制密切相关。目前已经报道的有关PI3K-Akt—mTOR通路抑制剂耐药机制，基本上可以分为与FOXO和激素受体相关，依赖于MYC，依赖于β-catenin，依赖于JAK／STAT通路，依赖于MAPK通路，及与AXL相关的耐药机制。PI3K—Akt—roTOR通路抑制剂的耐药，极大地影响了该类小分子靶向药物在临床上的使用，通过对其耐药性产生的机制进行探讨和总结，为临床上和其他药物联用克服该类靶向药物耐药提供策略。

英文摘要：

The resistance to PI3K-Akt-mTOR pathway inhibitors has close relationship to the negative feedback of its context-dependent signal pathways. According to our current understanding, the resistant mechanisms could be divided into the following basic conditions： related to FOXO and hormone receptor, MYC-dependence, β-catenin-dependence, JAK/STAT pathway-dependence, MAPK pathway-dependence and related to AXL. The emergence of drug resistance to PI3K-Akt-mTOR pathway inhibitors has greatly limited their curative effect. The reported resistance mechanisms to PI3K-Akt-mTOR pathway inhibitors to search for potential strategies for overcoming resistance by drug combination were summarized.