Laboratory of Receptor Cell Biology, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya Str., 16/10, 117997 Moscow, Russia.
Institute of Biochemistry and Signal Transduction, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany.
Int J Mol Sci. 2021 Feb 9;22(4):1743. doi: 10.3390/ijms22041743.
The aim of this review was to summarize current available information about the role of phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling in cancer as a potential target for new therapy options. The mTOR and PI3K/AKT/mTORC1 (mTOR complex 1) signaling are critical for the regulation of many fundamental cell processes including protein synthesis, cell growth, metabolism, survival, catabolism, and autophagy, and deregulated mTOR signaling is implicated in cancer, metabolic dysregulation, and the aging process. In this review, we summarize the information about the structure and function of the mTOR pathway and discuss the mechanisms of its deregulation in human cancers including genetic alterations of PI3K/AKT/mTOR pathway components. We also present recent data regarding the PI3K/AKT/mTOR inhibitors in clinical studies and the treatment of cancer, as well the attendant problems of resistance and adverse effects.
本次综述的目的是总结目前关于磷脂酰肌醇 3-激酶(PI3K)/AKT/哺乳动物雷帕霉素靶蛋白(mTOR)信号通路在癌症中的作用的信息,作为新治疗方案的潜在靶点。mTOR 和 PI3K/AKT/mTORC1(mTOR 复合物 1)信号通路对于许多基本细胞过程的调节至关重要,包括蛋白质合成、细胞生长、代谢、存活、分解代谢和自噬,而失调的 mTOR 信号通路与癌症、代谢失调和衰老过程有关。在本次综述中,我们总结了 mTOR 通路的结构和功能信息,并讨论了其在人类癌症中的失调机制,包括 PI3K/AKT/mTOR 通路成分的遗传改变。我们还介绍了最近关于 PI3K/AKT/mTOR 抑制剂在临床研究和癌症治疗中的应用,以及随之而来的耐药性和不良反应问题。