Pharmacotranscriptomic biomarkers in glucocorticoid treatment of pediatric inflammatory bowel disease

Lucafò M1, Stankovic B2, Kotur N2, Silvestre AD3, Martelossi S4, Ventura A1, Zukic B2, Pavlovic S5, Decorti G1. Curr Med Chem. 2017 Sep 20. doi: 10.2174/0929867324666170920145337. [Epub ahead of print]
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1 Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste. Italy. 2 Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade. Serbia. 3 PhD School in Science of Reproduction and Development, University of Trieste, Trieste. Italy. 4 Institute for Maternal and Child Health - IRCCS "Burlo Garofolo", Trieste. Italy. 5 Insitute of Molecular Genetics and Genetic Engineering Belgrade. Serbia.


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 the IBD treatment, GCs are still widely used for induction of remission in IBD 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 GCs activity. The aim of this review is to present the current knowledge of the role of the transcriptome in modulating GC response in pediatric IBD. 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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