Perspective: How complex in vitro models are addressing the challenges of predicting drug-induced liver injury
Predicting which drugs might have the potential to cause drug-induced liver injury (DILI) is highly complex and the current methods, 2D cell-based models and animal tests, are not sensitive enough to prevent some costly failures in clinical trials or to avoid all patient safety concerns for DILI pos...
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Frontiers Media S.A.
2025-02-01
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| Series: | Frontiers in Drug Discovery |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fddsv.2025.1536756/full |
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| author | K. Taylor R. Ram R. Ram L. Ewart C. Goldring G. Russomanno G. P. Aithal T. Kostrzewski C. Bauch J. M. Wilkinson J. M. Wilkinson S. Modi J. G. Kenna J. G. Kenna J. Bailey J. Bailey |
| author_facet | K. Taylor R. Ram R. Ram L. Ewart C. Goldring G. Russomanno G. P. Aithal T. Kostrzewski C. Bauch J. M. Wilkinson J. M. Wilkinson S. Modi J. G. Kenna J. G. Kenna J. Bailey J. Bailey |
| author_sort | K. Taylor |
| collection | DOAJ |
| description | Predicting which drugs might have the potential to cause drug-induced liver injury (DILI) is highly complex and the current methods, 2D cell-based models and animal tests, are not sensitive enough to prevent some costly failures in clinical trials or to avoid all patient safety concerns for DILI post-market. Animal-based methods are hampered by important species differences in metabolism and adaptive immunity compared to humans and the standard 2D in vitro approaches have limited metabolic functionality and complexity. On 24 April 2023 the Alliance for Human Relevant Science (https://www.humanrelevantscience.org/) hosted a workshop at the Royal Society, London entitled Drug-Induced Liver Injury (DILI): Can Human-Focused Testing Improve Clinical Translation? The conclusion was that complex in vitro models (CIVMs) provide a significant step forward in the safety testing paradigm. This perspective article, written by the participants, builds on those discussions to provide a ‘state of play’ on liver CIVMs with recommendations for how to encourage their greater uptake by the pharmaceutical industry. |
| format | Article |
| id | doaj-art-df583d12bd71495b8f42f31e2d3cda3d |
| institution | DOAJ |
| issn | 2674-0338 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Drug Discovery |
| spelling | doaj-art-df583d12bd71495b8f42f31e2d3cda3d2025-08-20T03:00:26ZengFrontiers Media S.A.Frontiers in Drug Discovery2674-03382025-02-01510.3389/fddsv.2025.15367561536756Perspective: How complex in vitro models are addressing the challenges of predicting drug-induced liver injuryK. Taylor0R. Ram1R. Ram2L. Ewart3C. Goldring4G. Russomanno5G. P. Aithal6T. Kostrzewski7C. Bauch8J. M. Wilkinson9J. M. Wilkinson10S. Modi11J. G. Kenna12J. G. Kenna13J. Bailey14J. Bailey15Independent Consultant, Sheffield, United KingdomSafer Medicines Trust, Kingsbridge, United KingdomAlliance for Human Relevant Science, London, United KingdomEmulate Inc., Boston, MA, United StatesDepartment of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, United KingdomDepartment of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, United KingdomNational Institute for Health Research (NIHR) Nottingham Biomedical Research Centre (BRC), Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, England, United KingdomCN-BIO, Cambridge, United KingdomCyprotex, Kalamazoo, MI, United StatesSchool of Chemical, Materials and Biological Engineering (CMBE), University of Sheffield, Sheffield, United Kingdom0Kirkstall Ltd, Sheffield, United Kingdom1Animal Free Research UK, London, United KingdomSafer Medicines Trust, Kingsbridge, United Kingdom2Independent Consultant, Macclesfield, United Kingdom1Animal Free Research UK, London, United Kingdom3The Physicians Committee, Washington, DC, United StatesPredicting which drugs might have the potential to cause drug-induced liver injury (DILI) is highly complex and the current methods, 2D cell-based models and animal tests, are not sensitive enough to prevent some costly failures in clinical trials or to avoid all patient safety concerns for DILI post-market. Animal-based methods are hampered by important species differences in metabolism and adaptive immunity compared to humans and the standard 2D in vitro approaches have limited metabolic functionality and complexity. On 24 April 2023 the Alliance for Human Relevant Science (https://www.humanrelevantscience.org/) hosted a workshop at the Royal Society, London entitled Drug-Induced Liver Injury (DILI): Can Human-Focused Testing Improve Clinical Translation? The conclusion was that complex in vitro models (CIVMs) provide a significant step forward in the safety testing paradigm. This perspective article, written by the participants, builds on those discussions to provide a ‘state of play’ on liver CIVMs with recommendations for how to encourage their greater uptake by the pharmaceutical industry.https://www.frontiersin.org/articles/10.3389/fddsv.2025.1536756/fullDILIliver injuryin vitro methodsanimal testingreplacementspheroids |
| spellingShingle | K. Taylor R. Ram R. Ram L. Ewart C. Goldring G. Russomanno G. P. Aithal T. Kostrzewski C. Bauch J. M. Wilkinson J. M. Wilkinson S. Modi J. G. Kenna J. G. Kenna J. Bailey J. Bailey Perspective: How complex in vitro models are addressing the challenges of predicting drug-induced liver injury Frontiers in Drug Discovery DILI liver injury in vitro methods animal testing replacement spheroids |
| title | Perspective: How complex in vitro models are addressing the challenges of predicting drug-induced liver injury |
| title_full | Perspective: How complex in vitro models are addressing the challenges of predicting drug-induced liver injury |
| title_fullStr | Perspective: How complex in vitro models are addressing the challenges of predicting drug-induced liver injury |
| title_full_unstemmed | Perspective: How complex in vitro models are addressing the challenges of predicting drug-induced liver injury |
| title_short | Perspective: How complex in vitro models are addressing the challenges of predicting drug-induced liver injury |
| title_sort | perspective how complex in vitro models are addressing the challenges of predicting drug induced liver injury |
| topic | DILI liver injury in vitro methods animal testing replacement spheroids |
| url | https://www.frontiersin.org/articles/10.3389/fddsv.2025.1536756/full |
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