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从生物标志物到治疗靶点——长非编码 RNA 在癌症中的前景与挑战。

From biomarkers to therapeutic targets-the promises and perils of long non-coding RNAs in cancer.

机构信息

Faculty of Medicine, Martin-Luther-University Halle-Wittenberg, 06120, Halle (Saale), Germany.

Institute of Experimental and Clinical Pharmacology, Medical University of Graz, 8010, Graz, Austria.

出版信息

Cancer Metastasis Rev. 2018 Mar;37(1):83-105. doi: 10.1007/s10555-017-9718-5.

Abstract

Biomarker-driven personalized cancer therapy is a field of growing interest, and several molecular tests have been developed to detect biomarkers that predict, e.g., response of cancers to particular therapies. Identification of these molecules and understanding their molecular mechanisms is important for cancer prognosis and the development of therapeutics for late stage diseases. In the past, significant efforts have been placed on the discovery of protein or DNA-based biomarkers while only recently the class of long non-coding RNA (lncRNA) has emerged as a new category of biomarker. The mammalian genome is pervasively transcribed yielding a vast amount of non-protein-coding RNAs including lncRNAs. Hence, these transcripts represent a rich source of information that has the potential to significantly contribute to precision medicine in the future. Importantly, many lncRNAs are differentially expressed in carcinomas and they are emerging as potent regulators of tumor progression and metastasis. Here, we will highlight prime examples of lncRNAs that serve as marker for cancer progression or therapy response and which might represent promising therapeutic targets. Furthermore, we will introduce lncRNA targeting tools and strategies, and we will discuss potential pitfalls in translating these into clinical trials.

摘要

基于生物标志物的个体化癌症治疗是一个日益受到关注的领域,已经开发出了几种分子检测方法来检测预测癌症对特定治疗反应的生物标志物。鉴定这些分子并了解它们的分子机制对于癌症预后以及晚期疾病治疗药物的开发非常重要。过去,人们在发现基于蛋白质或 DNA 的生物标志物方面做出了巨大的努力,而直到最近,长链非编码 RNA(lncRNA)才作为一种新的生物标志物类别出现。哺乳动物基因组广泛转录,产生大量非蛋白质编码 RNA,包括 lncRNA。因此,这些转录本代表了一个丰富的信息来源,有可能在未来为精准医疗做出重大贡献。重要的是,许多 lncRNA 在癌中表达不同,它们正在成为肿瘤进展和转移的有力调节因子。在这里,我们将重点介绍一些 lncRNA 的例子,它们可以作为癌症进展或治疗反应的标志物,并可能成为有前途的治疗靶点。此外,我们将介绍 lncRNA 靶向工具和策略,并讨论将它们转化为临床试验的潜在陷阱。

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