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近期针对mTOR的癌症治疗临床试验。

Recent clinical trials of mTOR-targeted cancer therapies.

作者信息

Don Aruni S Arachchige, Zheng X F Steven

机构信息

Cancer Institute of New Jersey and Department of Pharmacology, UMDNJ-Robert Wood, Johnson Medical School, Piscataway, NJ 08854, USA.

出版信息

Rev Recent Clin Trials. 2011 Jan;6(1):24-35. doi: 10.2174/157488711793980147.

Abstract

The mammalian target of rapamycin (mTOR) is a central component within a complex intracellular signaling network that regulates various processes including cell growth, proliferation, metabolism, and angiogenesis. A hyperactive PI3k/Akt/mTOR signaling pathway is found in many human cancers and alterations in this pathway is associated with the development and progression of cancer. Drugs that target and inhibit mTOR activity are therefore expected to provide therapeutic value in a number of cancer types. Several classes of mTOR-targeted therapeutics are currently being evaluated in cancer clinical trials, including the rapamycins, dual PI3K-mTOR inhibitors, and ATP-competitive mTORC1/2 inhibitors. This review summarizes important findings from recently completed trials of mTOR inhibitors and also discusses preliminary data from ongoing trials.

摘要

雷帕霉素的哺乳动物靶点(mTOR)是复杂的细胞内信号网络中的核心组成部分,该网络调节包括细胞生长、增殖、代谢和血管生成在内的各种过程。在许多人类癌症中发现PI3k/Akt/mTOR信号通路过度活跃,并且该通路的改变与癌症的发生和发展相关。因此,靶向并抑制mTOR活性的药物有望在多种癌症类型中提供治疗价值。目前有几类靶向mTOR的疗法正在癌症临床试验中进行评估,包括雷帕霉素、双PI3K-mTOR抑制剂和ATP竞争性mTORC1/2抑制剂。本综述总结了最近完成的mTOR抑制剂试验的重要发现,并讨论了正在进行的试验的初步数据。

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