摘要
背景:Pharmacotranscriptomics旨在根据个体间转录组变异达到更准确的药物剂量。 在这里,我们提供了RNA生物标志物的概述,可以预测糖皮质激素(GCs)的反应,被认为是治疗成人和儿童患者的炎症性肠病(IBD)的标准。 尽管新的生物制剂在IBD治疗中非常有效,但GC仍广泛用于诱导中度至重度疾病患者的缓解。 重要的是确定对GCs治疗反应差的患者,因为次优反应是频繁的并且与各种副作用相关。 已经研究了许多与GC作用机制相关的遗传变异。 但是,大多数报告的协会并不一致。 在这方面,药物基因组学研究正在探索RNA的世界。 适当调节转录组,主要包括控制基因表达的mRNA和非编码RNA对GC活性的调节具有强烈影响。 目的:本综述的目的是介绍转录组在调节儿童IBD中GC反应中的作用的现有知识。 结果:我们将讨论关于药代转录组生物标志物开发的现有文献,特别关注非编码RNA,并在该领域中展示结果,阐明将“组学”研究中获得的知识转化为临床实践的具体益处。
关键词: 糖皮质激素,药代动力学,炎症性肠病。 生物标志物,microRNA,长非编码RNA。
Current Medicinal Chemistry
Title:Pharmacotranscriptomic Biomarkers in Glucocorticoid Treatment of Pediatric Inflammatory Bowel Disease
Volume: 25 Issue: 24
关键词: 糖皮质激素,药代动力学,炎症性肠病。 生物标志物,microRNA,长非编码RNA。
摘要: Background: Pharmacotranscriptomics aims to reach more accurate drug dosing based on interindividual transcriptome variations. Here, we provide an overview of RNA biomarkers that could predict the response to glucocorticoids (GCs), considered the standard for treatment of inflammatory bowel diseases (IBD), both in adult and pediatric patients. Although new biological agents are very effective in IBD treatment, GCs are still widely used for induction of remission in patients with moderate to severe disease. It is important to identify patients that are poor responders to GCs therapy, because suboptimal response is frequent and associated with various side effects. A number of genetic variants related to GC mechanism of action has been studied. However, the majority of reported associations are not consistent. In this regard, pharmacogenomic research is now exploring the world of RNAs. An appropriate regulation of the transcriptome, which mainly comprises mRNAs and non-coding RNAs that control gene expression, has a strong impact in the modulation of GC activity.
Aim: The aim of this review is to present the current knowledge of the role of the transcriptome in modulating GC response in pediatric IBD.
Results: We will discuss the available literature, concerning the development of pharmacotranscriptomic biomarkers, focusing particularly on non-coding RNAs, and present the results in this field that elucidate a concrete benefit of translating the knowledge gained in the "omics" studies into clinical practice.
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Cite this article as:
Pharmacotranscriptomic Biomarkers in Glucocorticoid Treatment of Pediatric Inflammatory Bowel Disease, Current Medicinal Chemistry 2018; 25 (24) . https://dx.doi.org/10.2174/0929867324666170920145337
DOI https://dx.doi.org/10.2174/0929867324666170920145337 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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