1. Managing the challenge of drug-induced liver injury: a roadmap for the development and deployment of preclinical predictive models
- Author
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Raymond Pieters, Klaus Gjervig Jensen, Philip G. Hewitt, Jan Snoeys, Bob van de Water, B. Kevin Park, Ursula Klingmüller, André Guillouzo, Ian M. Copple, Dominic P. Williams, Michael J. Liguori, Cerys A. Lovatt, Paul Morgan, Satu Juhila, Eric A.G. Blomme, Magnus Ingelman-Sundberg, Dean J. Naisbitt, Gilles Labbe, Amy E. Chadwick, Christopher E. Goldring, Helga H.J. Gerets, Richard J. Weaver, Jonchère, Laurent, Mechanism-Based Integrated Systems for the Prediction of Drug-Induced Liver Injury - MIP-DILI - - EC:FP7:SP1-JTI2012-02-01 - 2017-01-31 - 115336 - VALID, University of Liverpool, Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Merck Research Laboratories, Karolinska Institutet [Stockholm], Division Systems Biology of Signal Transduction, German Cancer Research Center (DKFZ), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), SANOFI Recherche, Abbvie Inc. [North Chicago], GlaxoSmithKline, Glaxo Smith Kline, AstraZeneca, University Medical Center [Utrecht], Janssen Research & Development, Leiden University, Institut de Recherches Internationales Servier [Suresnes] (IRIS), UCB BioPharma [Braine l’Alleud, Belgium], This work was supported by the European Community (Contract MIP-DILI-115336) under the Innovative Medicines Initiative Joint Undertaking, a contribution from the European Union's Seventh Framework Programme (FP7/20072013) and European Federation of Pharmaceutical Industries and Associations (EFPIA) companies (http://www.imi.europa.eu/) and by the German Ministry of Education and Research (BMBF) within ‘Multi-Scale Modeling of Drug-Induced Liver Injury’ (MS_DILI, 031L0074A)., European Project: 115336,EC:FP7:SP1-JTI,IMI-JU-03-2010,MIP-DILI(2012), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), and Universiteit Leiden
- Subjects
0301 basic medicine ,Drug ,Drug-Related Side Effects and Adverse Reactions ,[SDV]Life Sciences [q-bio] ,media_common.quotation_subject ,In vitro model ,03 medical and health sciences ,Preclinical research ,0302 clinical medicine ,Predictive Value of Tests ,Drug Discovery ,Animals ,Humans ,Medicine ,media_common ,Pharmacology ,Adverse effects ,business.industry ,[SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology ,General Medicine ,[SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology ,3. Good health ,[SDV] Life Sciences [q-bio] ,Disease Models, Animal ,030104 developmental biology ,Risk analysis (engineering) ,Software deployment ,Preclinical testing ,030220 oncology & carcinogenesis ,Chemical and Drug Induced Liver Injury ,business - Abstract
International audience; Drug-induced liver injury (DILI) is a patient-specific, temporal, multifactorial pathophysiological process that cannot yet be recapitulated in a single in vitro model. Current preclinical testing regimes for the detection of human DILI thus remain inadequate. A systematic and concerted research effort is required to address the deficiencies in current models and to present a defined approach towards the development of new or adapted model systems for DILI prediction. This Perspective defines the current status of available models and the mechanistic understanding of DILI, and proposes our vision of a roadmap for the development of predictive preclinical models of human DILI.
- Published
- 2019