title: Towards better models and mechanistic biomarkers for drug-induced gastrointestinal injury.
abstract: Adverse drug reactions affecting the gastrointestinal (GI) tract are a serious burden on patients, healthcare providers and the pharmaceutical industry. GI toxicity encompasses a range of pathologies in different parts of the GI tract. However, to date no specific mechanistic diagnostic/prognostic biomarkers or translatable pre-clinical models of GI toxicity exist. This review will cover the current knowledge of GI ADRs, existing biomarkers and models with potential application for toxicity screening/monitoring. We focus on the current gaps in our knowledge, the potential opportunities and recommend that a systematic approach is needed to identify mechanism-based GI biomarkers with potential for clinical translation.
authors.affiliation: MRC Centre for Drug Safety Science, Department of Clinical and Molecular Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK. Electronic address: d.carr@liverpool.ac.uk.
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Carr
authors.affiliation: MatTek Corporation, Ashland, MA, USA.
authors.forename: Seyoum
authors.initials: S
authors.lastname: Ayehunie
authors.affiliation: MRC Centre for Drug Safety Science, Department of Clinical and Molecular Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
authors.forename: Andrea
authors.initials: A
authors.lastname: Davies
authors.affiliation: Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool L69 3GE, UK.
authors.forename: Carrie A
authors.initials: CA
authors.lastname: Duckworth
authors.affiliation: MRC Centre for Drug Safety Science, Department of Clinical and Molecular Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
authors.forename: Stephanie
authors.initials: S
authors.lastname: French
authors.affiliation: Department of Comparative and Functional Genomics, Institute of Integrative Biology, University of Liverpool, Liverpool L69 7ZB, UK.
authors.forename: Neil
authors.initials: N
authors.lastname: Hall
authors.affiliation: Department of Molecular and Clinical Cancer Medicine Institute of Translational Medicine, University of Liverpool, Liverpool L69 3GA, UK.
authors.forename: Syed
authors.initials: S
authors.lastname: Hussain
authors.affiliation: Vertex Pharmaceuticals (Europe), Abingdon, Oxfordshire, UK.
authors.forename: Howard R
authors.initials: HR
authors.lastname: Mellor
authors.affiliation: MRC Centre for Drug Safety Science, Department of Clinical and Molecular Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
authors.forename: Alan
authors.initials: A
authors.lastname: Norris
authors.affiliation: MRC Centre for Drug Safety Science, Department of Clinical and Molecular Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
authors.forename: B Kevin
authors.initials: BK
authors.lastname: Park
authors.affiliation: MRC Centre for Drug Safety Science, Department of Clinical and Molecular Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
authors.forename: Alexander
authors.initials: A
authors.lastname: Penrose
authors.affiliation: Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool L69 3GE, UK.
authors.forename: D Mark
authors.initials: DM
authors.lastname: Pritchard
authors.affiliation: Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool L69 3GE, UK.
authors.forename: Chris S
authors.initials: CS
authors.lastname: Probert
authors.affiliation: Pfizer Inc, Cambridge, MA, USA.
authors.forename: Shashi
authors.initials: S
authors.lastname: Ramaiah
authors.affiliation: ApconiX, Alderley Edge, Cheshire, UK.
authors.forename: Claire
authors.initials: C
authors.lastname: Sadler
authors.affiliation: Merck KGaA, Darmstadt, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Schmitt
authors.affiliation: Medicines & Healthcare Products Regulatory Agency, London, UK.
authors.forename: Alison
authors.initials: A
authors.lastname: Shaw
authors.affiliation: Phenotox Ltd, Bollington, Cheshire, UK.
authors.forename: James E
authors.initials: JE
authors.lastname: Sidaway
authors.affiliation: Hubrecht Organoid Technology, Utrecht, The Netherlands.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Vries
authors.affiliation: AstraZeneca Pharmaceuticals, Innovative Medicines and Early Development, Drug Safety and Metabolism, Waltham, MA, United States.
authors.forename: Matthew
authors.initials: M
authors.lastname: Wagoner
authors.affiliation: MRC Centre for Drug Safety Science, Department of Clinical and Molecular Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
authors.forename: Munir
authors.initials: M
authors.lastname: Pirmohamed
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015195:Drug Design; D055808:Drug Discovery / Q000379:methods; D004353:Drug Evaluation, Preclinical / Q000379:methods; D064420:Drug-Related Side Effects and Adverse Reactions / Q000175:diagnosis*; D005767:Gastrointestinal Diseases / Q000139:chemically induced* / Q000503:physiopathology; D006801:Humans; D008954:Models, Biological; D018675:Toxicity Tests / Q000379:methods
chemical_list: D015415:Biomarkers
keywords: Adverse drug reaction; Biomarker; Gastrointestinal; In vitro; In vivo; Toxicity