Tailoring mTOR-based therapy: molecular evidence and clinical challenges.

Tailoring mTOR-based therapy: molecular evidence and clinical challenges.
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DOI:
10.2217/pgs.13.143
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发表时间:
2013-09
期刊:
影响因子:
2.1
通讯作者:
Totary-Jain H
Totary-Jain H
中科院分区:
医学4区
文献类型:
--
作者:
Santulli G;Totary-Jain H

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mTOR信号通路整合了来自各种上游刺激的输入以调节不同的细胞过程,包括增殖、生长、存活、运动、自噬、蛋白质合成和代谢。mTOR通路在许多人类病理学中失调,包括癌症、糖尿病、肥胖症、自身免疫性疾病、神经疾病和衰老。目前正在进行的mTOR靶向治疗的临床试验有数百项,并强调了其治疗潜力。迄今为止,mTOR抑制剂在临床上被批准用于预防器官排斥,抑制血管成形术后的再狭窄,以及治疗几种晚期癌症。在这篇综述中,我们讨论了不断发展的mTOR药物基因组学领域,并强调了在识别诊断和预后标志物(包括miRNA)方面的新兴努力,以评估成功的治疗反应。
The mTOR signaling pathway integrates inputs from a variety of upstream stimuli to regulate diverse cellular processes including proliferation, growth, survival, motility, autophagy, protein synthesis and metabolism. The mTOR pathway is dysregulated in a number of human pathologies including cancer, diabetes, obesity, autoimmune disorders, neurological disease and aging. Ongoing clinical trials testing mTOR-targeted treatments number in the hundreds and underscore its therapeutic potential. To date mTOR inhibitors are clinically approved to prevent organ rejection, to inhibit restenosis after angioplasty, and to treat several advanced cancers. In this review we discuss the continuously evolving field of mTOR pharmacogenomics, as well as highlight the emerging efforts in identifying diagnostic and prognostic markers, including miRNAs, in order to assess successful therapeutic responses.
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