中文摘要：

mTOR是处于调节细胞代谢、生长、增殖等整个过程中心环节的重要激酶.干扰或抑制mTOR会引起细胞尤其是癌细胞的生长停滞继而死亡.因而也被公认为是癌症治疗当中的一个潜在靶标.一系列的mTOR抑制剂Rapamycin及类似物已经形成并在临床抗肿瘤中有所应用,但其展示的效应非常有限.随着研究的深入,发现mTOR信号通路存在反馈激活机制：即抑制mTOR能反馈性激活多个与细胞生长增殖相关的信号通路.并且认为是这些反馈激活机制削弱了mTOR抑制荆的效能.也是其临床效应未达预期的原因.本文就目前国内外研究较深入的mTOR-AKT,mTOR-ERK,mTOR-elF4E反馈信号通路做详细概述.并阐述目前采取的防止这一反馈机制形成的Rapamycin类似物与特定通路抑制剂的联合用药策略,使mTOR抑制剂在临床抗肿瘤中能充分发挥其效能.

英文摘要：

mTOR is a very important kinase which plays a central role in regulating cell metabolism, growth, and proliferation. Interfering or inhibiting mTOR activity would stop cell growth and subsequently, death in normal cells, especially in cancer cells. Therefore, mTOR has been considered as a critical potential target for cancer therapy. Subsequently, a series of mTOR inhibitors have already been invented and tested in clinics. However, an anti-tumor effect was not indicated as expected. Therefore, it was thought that some factors blocking the mTOR pathway and considerably weakening the clinical efficacy of its inhibitors must be in existence. After intensive studies, feedback mechanisms of mTOR signaling pathway were identified. Simultaneously, the inhibition of roTOR has been observed to activate multi pathways related to cell growth and proliferation. Thus, the feedback mechanisms were regarded as the direct reasons that attenuated the efficacy of mTOR inhibitors and resulted in unsatisfactory clinical effects. In the present paper, the feedback-activated pathways of mTOR-AKT, mTOR-ERK, and mTOR-eIF4E will be discussed in detail, as well as other strategies that rapamycin analogs and specified pathway inhibitors can be combined to treat cancer. The present paper is aimed to fully discuss the potential antitumor activity of roTOR inhibitors.