Medical Oncology 1, IRCCS-Regina Elena National Cancer Institute, Rome, Italy.
SAFU, Department of Research, Advanced Diagnostics, and Technological Innovation, IRCCS-Regina Elena National Cancer Institute, Rome, Italy.
Adv Exp Med Biol. 2020;1223:69-80. doi: 10.1007/978-3-030-35582-1_4.
The mammalian target of rapamycin (mTOR) represents a critical hub for the regulation of different processes in both normal and tumor cells. Furthermore, it is now well established the role of mTOR in integrating and shaping different environmental paracrine and autocrine stimuli in tumor microenvironment (TME) constituents. Recently, further efforts have been employed to understand how the mTOR signal transduction mechanisms modulate the sensitivity and resistance to targeted therapies, also for its involvement of mTOR also in modulating angiogenesis and tumor immunity. Indeed, interest in mTOR targeting was increased to improve immune response against cancer and to develop new long-term efficacy strategies, as demonstrated by clinical success of mTOR and immune checkpoint inhibitor combinations. In this chapter, we will describe the role of mTOR in modulating TME elements and the implication in its targeting as a great promise in clinical trials.
哺乳动物雷帕霉素靶蛋白(mTOR)是调节正常和肿瘤细胞中不同过程的关键枢纽。此外,现在已经明确 mTOR 在整合和塑造肿瘤微环境(TME)成分中的不同环境旁分泌和自分泌刺激中的作用。最近,人们进一步努力了解 mTOR 信号转导机制如何调节对靶向治疗的敏感性和耐药性,这也是因为 mTOR 也参与调节血管生成和肿瘤免疫。事实上,人们对 mTOR 靶向治疗的兴趣增加了,以提高对癌症的免疫反应,并开发新的长期疗效策略,mTOR 和免疫检查点抑制剂联合的临床成功证明了这一点。在本章中,我们将描述 mTOR 在调节 TME 成分中的作用及其作为临床试验中巨大希望的靶向作用的意义。