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Nat Rev Drug Discov. 2016 Nov;15(11):751-769. doi: 10.1038/nrd.2016.175. Epub 2016 Sep 12.

Screening out irrelevant cell-based models of disease.

Author information

1
Synthetic and Systems Biology Unit, Biological Research Centre of the Hungarian Academy of Sciences, Szeged H-6726, Hungary; and at the Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki 00290, Finland.
2
European Cell-Based Assays Interest Group.
3
Imagopole-Citech, Institut Pasteur, Paris 75015, France.
4
Technology Development Studio, Max Planck Institute of Molecular Cell Biology and Genetics, Dresden 01307, Germany.
5
Translational Cell Imaging Queensland (TCIQ), Institute of Health Biomedical Innovation, Queensland University of Technology, Brisbane 4102 QLD, Australia; and The Irish National Centre for High Content Screening and Analysis, Trinity Translational Medicine Institute, Trinity College Dublin, Phase 3 Trinity Health Sciences 1.20, St James Hospital, Dublin D8, Republic of Ireland.
6
Institut Curie, PSL Research University, Department of Translational Research, The Biophenics High-Content Screening Laboratory, Cell and Tissue Imaging Facility (PICT-IBiSA), F-75005, Paris, France.
7
Target Discovery Institute, University of Oxford, Oxford OX3 7FZ, UK.
8
Cellomics Unit, Cell Biology &Physiology Program, Cell &Developmental Biology Area, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid 28029, Spain.
9
Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki 00290, Finland.
10
Science for Life Laboratory, Department of Oncology and Pathology, Karolinska Institutet, Stockholm 17165, Sweden.
11
Faculty of Science, Leiden Academic Centre for Drug Research, Toxicology, Universiteit Leiden, The Netherlands; and at OcellO, J.H Oortweg 21, 2333 CH, Leiden, The Netherlands.
12
Biomolecular Screening Facility, Swiss Federal Institute of Technology (EPFL), Lausanne CH-1015, Switzerland.
13
Cancer Research UK Edinburgh Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XR, UK.

Abstract

The common and persistent failures to translate promising preclinical drug candidates into clinical success highlight the limited effectiveness of disease models currently used in drug discovery. An apparent reluctance to explore and adopt alternative cell- and tissue-based model systems, coupled with a detachment from clinical practice during assay validation, contributes to ineffective translational research. To help address these issues and stimulate debate, here we propose a set of principles to facilitate the definition and development of disease-relevant assays, and we discuss new opportunities for exploiting the latest advances in cell-based assay technologies in drug discovery, including induced pluripotent stem cells, three-dimensional (3D) co-culture and organ-on-a-chip systems, complemented by advances in single-cell imaging and gene editing technologies. Funding to support precompetitive, multidisciplinary collaborations to develop novel preclinical models and cell-based screening technologies could have a key role in improving their clinical relevance, and ultimately increase clinical success rates.

PMID:
27616293
DOI:
10.1038/nrd.2016.175
[Indexed for MEDLINE]

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