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mRNA 翻译在癌症中的生物学和治疗相关性。

The biological and therapeutic relevance of mRNA translation in cancer.

机构信息

Department of Oncology, Imperial College Hammersmith Campus, Du Cane Road, London W12 0HS, UK. s.blagden@ imperial.ac.uk

出版信息

Nat Rev Clin Oncol. 2011 May;8(5):280-91. doi: 10.1038/nrclinonc.2011.16. Epub 2011 Mar 1.

Abstract

Protein synthesis is a tightly regulated process that enables post-transcriptional control of gene expression. Dysregulation of this process is associated with the development and progression of cancers because components of the translational machinery function at the point of convergence of aberrant cell signaling pathways. Drugs designed to inhibit mRNA translation are currently in preclinical and early clinical development, and are likely to provide effective anticancer strategies in the future. In this Review, we summarize the main components of translation and describe how alterations in these proteins and their principle upstream signaling pathways can impact on cancer. The first inhibitors of translation, drugs designed to target eIF4E, have been trialed in hematologic malignancies, while antisense oligonucleotides against eIF4E are also due to enter clinical trials. Here, we discuss the mode of action of drugs designed to inhibit mRNA translation and other promising therapies that are in preclinical development with the aim of becoming anticancer agents.

摘要

蛋白质合成是一个受到严格调控的过程,它能够实现基因表达的转录后控制。这个过程的失调与癌症的发生和发展有关,因为翻译机制的组件在异常细胞信号通路的汇聚点发挥作用。目前,旨在抑制 mRNA 翻译的药物正在进行临床前和早期临床开发,并且很可能在未来提供有效的抗癌策略。在这篇综述中,我们总结了翻译的主要成分,并描述了这些蛋白质及其主要上游信号通路的改变如何影响癌症。第一批针对翻译的抑制剂,旨在针对 eIF4E 的药物,已经在血液恶性肿瘤中进行了试验,而针对 eIF4E 的反义寡核苷酸也即将进入临床试验。在这里,我们讨论了旨在抑制 mRNA 翻译的药物以及其他具有前景的、正在临床前开发阶段的治疗方法的作用机制,旨在成为抗癌药物。

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