Long-noncoding RNAs (lncRNAs) in drug metabolism and disposition, implications in cancer chemo-resistance

Drug metabolism is an orchestrated process in which drugs are metabolized and disposed through a series of specialized enzymes and transporters. Alterations in the expression and/or activity of these enzymes and transporters can affect the bioavailability (pharmacokinetics, or PK) and therapeutic ef...

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Bibliographic Details
Published in:Acta pharmaceutica Sinica. B 2020-01, Vol.10 (1), p.105-112
Main Authors: Wang, Yue, Fang, Zihui, Hong, Mei, Yang, Da, Xie, Wen
Format: Article
Language:English
Subjects:
Chemo-resistance
Drug metabolism
LncRNA
Regulation
Review
Xenobiotic receptor
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Summary:Drug metabolism is an orchestrated process in which drugs are metabolized and disposed through a series of specialized enzymes and transporters. Alterations in the expression and/or activity of these enzymes and transporters can affect the bioavailability (pharmacokinetics, or PK) and therapeutic efficacy (pharmacodynamics, or PD) of drugs. Recent studies have suggested that the long non-coding RNAs (lncRNAs) are highly relevant to drug metabolism and drug resistance, including chemo-resistance in cancers, through the regulation of drug metabolism and disposition related genes. This review summarizes the regulation of enzymes, transporters, or regulatory proteins involved in drug metabolism by lncRNAs, with a particular emphasis on drug metabolism and chemo-resistance in cancer patients. The perspective strategies to integrate multi-dimensional pharmacogenomics data for future in-depth analysis of drug metabolism related lncRNAs are also proposed. Understanding the role of lncRNAs in drug metabolism will not only facilitate the identification of novel regulatory mechanisms, but also enable the discovery of lncRNA-based biomarkers and drug targets to personalize and improve the therapeutic outcome of patients, including cancer patients. Drug metabolism and disposition affect drug bioavailability and efficacy. Emerging evidence has pointed an essential role of long non-coding RNAs (lncRNAs) in regulating drug metabolism and disposition. This review summarizes current understanding of the mechanism by which lncRNAs regulate drug metabolism and disposition, and implications of this regulation in chemo-resistance. [Display omitted]
ISSN:2211-3835
2211-3843
DOI:10.1016/j.apsb.2019.09.011