摘要
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(IncRNAs)are highly relevant to drug metabolism and drug resistance,including chemoresistance 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 IncRNAs,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 IncRNAs are also proposed.Understanding the role of IncRNAs in drug metabolism will not only facilitate the identification of novel regulatory mechanisms,but also enable the discovery of IncRNA-based biomarkers and drug targets to personalize and improve the therapeutic outcome of patients,including cancer patients.
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 (IncRNAs) are highly relevant to drug metabolism and drug resistance,including chemoresistance 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 IncRNAs,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 IncRNAs are also proposed.Understanding the role of IncRNAs in drug metabolism will not only facilitate the identification of novel regulatory mechanisms,but also enable the discovery of IncRNA-based biomarkers and drug targets to personalize and improve the therapeutic outcome of patients,including cancer patients.
基金
supported in part by NIH grant ES030429(to W.X.)and CA222274(to D.Y.)
supported in part by the Joseph Koslow Endowed Professorship from the University of Pittsburgh School of Pharmacy.
