Department of Molecular Oncology, King Faisal Specialist Hospital & Research Centre, PO Box 3354, Research Center (MBC 03), Riyadh, 11211, Saudi Arabia.
Semin Cancer Biol. 2019 Dec;59:92-111. doi: 10.1016/j.semcancer.2019.07.003. Epub 2019 Aug 10.
Mammalian target of rapamycin (mTOR) is a serine/threonine kinase that gets inputs from the amino acids, nutrients, growth factor, and environmental cues to regulate varieties of fundamental cellular processes which include protein synthesis, growth, metabolism, aging, regeneration, autophagy, etc. The mTOR is frequently deregulated in human cancer and activating somatic mutations of mTOR were recently identified in several types of human cancer and hence mTOR is therapeutically targeted. mTOR inhibitors were commonly used as immunosuppressors and currently, it is approved for the treatment of human malignancies. This review briefly focuses on the structure and biological functions of mTOR. It extensively discusses the genetic deregulation of mTOR including amplifications and somatic mutations, mTOR-mediated cell growth promoting signaling, therapeutic targeting of mTOR and the mechanisms of resistance, the role of mTOR in precision medicine and other recent advances in further understanding the role of mTOR in cancer.
哺乳动物雷帕霉素靶蛋白(mTOR)是一种丝氨酸/苏氨酸激酶,它从氨基酸、营养物质、生长因子和环境线索中获取信息,调节各种基本细胞过程,包括蛋白质合成、生长、代谢、衰老、再生、自噬等。mTOR 在人类癌症中经常失调,最近在几种人类癌症中发现了 mTOR 的激活体细胞突变,因此 mTOR 是治疗的靶点。mTOR 抑制剂通常被用作免疫抑制剂,目前已被批准用于治疗人类恶性肿瘤。本文简要介绍了 mTOR 的结构和生物学功能。它广泛讨论了 mTOR 的遗传失调,包括扩增和体细胞突变、mTOR 介导的细胞生长促进信号、mTOR 的治疗靶向以及耐药机制、mTOR 在精准医学中的作用以及进一步理解 mTOR 在癌症中的作用的最新进展。