Department of Experimental, Diagnostic and Specialty Medicine, S.Orsola-Malpighi University Hospital, 40138 Bologna, Italy.
Nuclear Medicine Unit, Medicina Nucleare Metropolitana, S.Orsola-Malpighi University Hospital, 40138 Bologna, Italy.
Int J Mol Sci. 2018 Mar 6;19(3):747. doi: 10.3390/ijms19030747.
The mechanistic target of rapamycin (mTOR) is part of the phosphoinositide-3-kinase (PI3K)/protein kinase B (AkT)/mTOR pathway and owes its name to the inhibitory effect of rapamycin. The mTOR has a central converging role for many cell functions, serving as a sensor for extracellular signals from energy status and nutrients availability, growth factors, oxygen and stress. Thus, it also modulates switch to anabolic processes (protein and lipid synthesis) and autophagy, in order to regulate cell growth and proliferation. Given its functions in the cell, its deregulation is implicated in many human diseases, including cancer. Its predominant role in tumorigenesis and progression of neuroendocrine tumors (NETs), in particular, has been demonstrated in preclinical studies and late clinical trials. mTOR inhibition by everolimus is an established therapeutic target in NETs, but there are no identified predictive or prognostic factors. This review is focused on the role of mTOR and everolimus in NETs, from preclinical studies to major clinical trials, and future perspectives involving mTOR in the treatment of NETs.
雷帕霉素靶蛋白（mTOR）是磷酸肌醇 3-激酶（PI3K）/蛋白激酶 B（Akt）/mTOR 通路的一部分，其名称来源于雷帕霉素的抑制作用。mTOR 在许多细胞功能中具有中心汇聚作用，作为细胞外信号（能量状态和营养物质可用性、生长因子、氧气和应激）的传感器。因此，它还调节向合成代谢过程（蛋白质和脂质合成）和自噬的转变，以调节细胞生长和增殖。鉴于其在细胞中的功能，其失调与许多人类疾病有关，包括癌症。在临床前研究和后期临床试验中已经证明，mTOR 在神经内分泌肿瘤（NETs）的肿瘤发生和进展中起主要作用。依维莫司抑制 mTOR 是 NETs 的一种既定治疗靶点，但目前尚无确定的预测或预后因素。这篇综述重点介绍了 mTOR 和依维莫司在 NETs 中的作用，从临床前研究到主要临床试验，以及涉及 mTOR 在 NETs 治疗中的未来前景。
