Islamic Azad University, Tehran Medical Sciences Branch, Tehran, Iran.
Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran.
DNA Repair (Amst). 2021 Aug;104:103142. doi: 10.1016/j.dnarep.2021.103142. Epub 2021 Jun 3.
The mammalian target of rapamycin (mTOR) is a conserved serine/threonine-protein kinase, comprising two subunit protein complexes: mTORC1 and mTORC2. In response to insult and cancer, the mTOR pathway plays a crucial role in regulating growth, metabolism, cell survival, and protein synthesis. Key subunits of mTORC1/2 catalyze the phosphorylation of various molecules, including eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1), ribosomal protein S6 kinase β-1 (S6K1). The DNA damage response (DDR) maintains genomic stability and provides an opportunity for treating tumors with defects caused by DNA damaging agents. Many mTOR inhibitors are utilized for the treatment of cancers. However, several clinical trials are still assessing the efficacy of mTOR inhibitors. This paper discusses the role of the mTOR signaling pathway and its regulators in developing cancer. In the following, we will review the interaction between DDR and mTOR signaling and the innovative therapies applied in preclinical and clinical trials for treating cancers.
哺乳动物雷帕霉素靶蛋白（mTOR）是一种保守的丝氨酸/苏氨酸蛋白激酶，由两个亚基蛋白复合物组成：mTORC1 和 mTORC2。在应对损伤和癌症时，mTOR 通路在调节生长、代谢、细胞存活和蛋白质合成方面起着至关重要的作用。mTORC1/2 的关键亚基催化各种分子的磷酸化，包括真核翻译起始因子 4E 结合蛋白 1（4E-BP1）、核糖体蛋白 S6 激酶β-1（S6K1）。DNA 损伤反应（DDR）维持基因组稳定性，并为治疗因 DNA 损伤剂引起的肿瘤缺陷提供了机会。许多 mTOR 抑制剂被用于癌症的治疗。然而，仍有几项临床试验在评估 mTOR 抑制剂的疗效。本文讨论了 mTOR 信号通路及其调节剂在癌症发展中的作用。在接下来的内容中，我们将回顾 DDR 与 mTOR 信号之间的相互作用，以及在临床前和临床试验中应用于治疗癌症的创新疗法。
