Screening out irrelevant cell-based models of disease.
Identifieur interne : 001755 ( Main/Merge ); précédent : 001754; suivant : 001756Screening out irrelevant cell-based models of disease.
Auteurs : Peter Horvath [Finlande] ; Nathalie Aulner [France] ; Marc Bickle [Allemagne] ; Anthony M. Davies ; Elaine Del Nery [France] ; Daniel Ebner [Royaume-Uni] ; Maria C. Montoya [Espagne] ; P Ivi Östling [Finlande] ; Vilja Pieti Inen [Finlande] ; Leo S. Price [Pays-Bas] ; Spencer L. Shorte [France] ; Gerardo Turcatti [Suisse] ; Carina Von Schantz [Finlande] ; Neil O. Carragher [Royaume-Uni]Source :
- Nature reviews. Drug discovery [ 1474-1784 ] ; 2016.
Descripteurs français
- KwdFr :
- Animaux, Cellules souches pluripotentes induites (), Cellules souches pluripotentes induites (physiologie), Découverte de médicament (), Humains, Lignée de cellules transformées, Modèles biologiques, Préparations pharmaceutiques (administration et posologie), Techniques de culture cellulaire (), Tests de criblage à haut débit (), Évaluation préclinique de médicament ().
- MESH :
- administration et posologie : Préparations pharmaceutiques.
- physiologie : Cellules souches pluripotentes induites.
- Animaux, Cellules souches pluripotentes induites, Découverte de médicament, Humains, Lignée de cellules transformées, Modèles biologiques, Techniques de culture cellulaire, Tests de criblage à haut débit, Évaluation préclinique de médicament.
English descriptors
- KwdEn :
- Animals, Cell Culture Techniques (methods), Cell Line, Transformed, Drug Discovery (methods), Drug Evaluation, Preclinical (methods), High-Throughput Screening Assays (methods), Humans, Induced Pluripotent Stem Cells (drug effects), Induced Pluripotent Stem Cells (physiology), Models, Biological, Pharmaceutical Preparations (administration & dosage).
- MESH :
- chemical , administration & dosage : Pharmaceutical Preparations.
- drug effects : Induced Pluripotent Stem Cells.
- methods : Cell Culture Techniques, Drug Discovery, Drug Evaluation, Preclinical, High-Throughput Screening Assays.
- physiology : Induced Pluripotent Stem Cells.
- Animals, Cell Line, Transformed, Humans, Models, Biological.
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.
DOI: 10.1038/nrd.2016.175
PubMed: 27616293
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Screening out irrelevant cell-based models of disease.</title><author><name sortKey="Horvath, Peter" sort="Horvath, Peter" uniqKey="Horvath P" first="Peter" last="Horvath">Peter Horvath</name><affiliation wicri:level="4"><nlm:affiliation>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.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>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</wicri:regionArea><orgName type="university">Université d'Helsinki</orgName><placeName><settlement type="city">Helsinki</settlement><region type="région" nuts="2">Uusimaa</region></placeName></affiliation></author><author><name sortKey="Aulner, Nathalie" sort="Aulner, Nathalie" uniqKey="Aulner N" first="Nathalie" last="Aulner">Nathalie Aulner</name><affiliation wicri:level="1"><nlm:affiliation>Imagopole-Citech, Institut Pasteur, Paris 75015, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Imagopole-Citech, Institut Pasteur, Paris 75015</wicri:regionArea><wicri:noRegion>75015</wicri:noRegion><placeName><settlement type="city">Paris</settlement><region type="région" nuts="2">Île-de-France</region></placeName></affiliation></author><author><name sortKey="Bickle, Marc" sort="Bickle, Marc" uniqKey="Bickle M" first="Marc" last="Bickle">Marc Bickle</name><affiliation wicri:level="3"><nlm:affiliation>Technology Development Studio, Max Planck Institute of Molecular Cell Biology and Genetics, Dresden 01307, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Technology Development Studio, Max Planck Institute of Molecular Cell Biology and Genetics, Dresden 01307</wicri:regionArea><placeName><region type="land" nuts="1">Saxe (Land)</region><region type="district" nuts="2">District de Dresde</region><settlement type="city">Dresde</settlement></placeName></affiliation></author><author><name sortKey="Davies, Anthony M" sort="Davies, Anthony M" uniqKey="Davies A" first="Anthony M" last="Davies">Anthony M. 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Price</name><affiliation wicri:level="3"><nlm:affiliation>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.</nlm:affiliation><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Faculty of Science, Leiden Academic Centre for Drug Research, Toxicology, Universiteit Leiden, The Netherlands; and at OcellO, J.H Oortweg 21, 2333 CH, Leiden</wicri:regionArea><placeName><settlement type="city">Leyde</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Shorte, Spencer L" sort="Shorte, Spencer L" uniqKey="Shorte S" first="Spencer L" last="Shorte">Spencer L. 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Davies</name><affiliation><nlm:affiliation>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.</nlm:affiliation><wicri:noCountry code="subField">Republic of Ireland</wicri:noCountry></affiliation></author><author><name sortKey="Nery, Elaine Del" sort="Nery, Elaine Del" uniqKey="Nery E" first="Elaine Del" last="Nery">Elaine Del Nery</name><affiliation wicri:level="3"><nlm:affiliation>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.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>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</wicri:regionArea><placeName><settlement type="city">Paris</settlement><region type="région" nuts="2">Île-de-France</region></placeName></affiliation></author><author><name sortKey="Ebner, Daniel" sort="Ebner, Daniel" uniqKey="Ebner D" first="Daniel" last="Ebner">Daniel Ebner</name><affiliation wicri:level="4"><nlm:affiliation>Target Discovery Institute, University of Oxford, Oxford OX3 7FZ, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Target Discovery Institute, University of Oxford, Oxford OX3 7FZ</wicri:regionArea><orgName type="university">Université d'Oxford</orgName><placeName><settlement type="city">Oxford</settlement><region type="nation">Angleterre</region><region type="région" nuts="1">Oxfordshire</region></placeName></affiliation></author><author><name sortKey="Montoya, Maria C" sort="Montoya, Maria C" uniqKey="Montoya M" first="Maria C" last="Montoya">Maria C. Montoya</name><affiliation wicri:level="1"><nlm:affiliation>Cellomics Unit, Cell Biology &Physiology Program, Cell &Developmental Biology Area, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid 28029, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Cellomics Unit, Cell Biology &Physiology Program, Cell &Developmental Biology Area, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid 28029</wicri:regionArea><placeName><settlement type="city">Madrid</settlement><region nuts="2" type="region">Communauté de Madrid</region></placeName></affiliation></author><author><name sortKey="Ostling, P Ivi" sort="Ostling, P Ivi" uniqKey="Ostling P" first="P Ivi" last="Östling">P Ivi Östling</name><affiliation wicri:level="4"><nlm:affiliation>Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki 00290, Finland.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki 00290</wicri:regionArea><orgName type="university">Université d'Helsinki</orgName><placeName><settlement type="city">Helsinki</settlement><region type="région" nuts="2">Uusimaa</region></placeName></affiliation></author><author><name sortKey="Pieti Inen, Vilja" sort="Pieti Inen, Vilja" uniqKey="Pieti Inen V" first="Vilja" last="Pieti Inen">Vilja Pieti Inen</name><affiliation wicri:level="4"><nlm:affiliation>Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki 00290, Finland.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki 00290</wicri:regionArea><orgName type="university">Université d'Helsinki</orgName><placeName><settlement type="city">Helsinki</settlement><region type="région" nuts="2">Uusimaa</region></placeName></affiliation></author><author><name sortKey="Price, Leo S" sort="Price, Leo S" uniqKey="Price L" first="Leo S" last="Price">Leo S. Price</name><affiliation wicri:level="3"><nlm:affiliation>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.</nlm:affiliation><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Faculty of Science, Leiden Academic Centre for Drug Research, Toxicology, Universiteit Leiden, The Netherlands; and at OcellO, J.H Oortweg 21, 2333 CH, Leiden</wicri:regionArea><placeName><settlement type="city">Leyde</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Shorte, Spencer L" sort="Shorte, Spencer L" uniqKey="Shorte S" first="Spencer L" last="Shorte">Spencer L. Shorte</name><affiliation wicri:level="3"><nlm:affiliation>Imagopole-Citech, Institut Pasteur, Paris 75015, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Imagopole-Citech, Institut Pasteur, Paris 75015</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region></placeName></affiliation></author><author><name sortKey="Turcatti, Gerardo" sort="Turcatti, Gerardo" uniqKey="Turcatti G" first="Gerardo" last="Turcatti">Gerardo Turcatti</name><affiliation wicri:level="1"><nlm:affiliation>Biomolecular Screening Facility, Swiss Federal Institute of Technology (EPFL), Lausanne CH-1015, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Biomolecular Screening Facility, Swiss Federal Institute of Technology (EPFL), Lausanne CH-1015</wicri:regionArea><placeName><settlement type="city">Lausanne</settlement><region nuts="3" type="region">Canton de Vaud</region></placeName></affiliation></author><author><name sortKey="Von Schantz, Carina" sort="Von Schantz, Carina" uniqKey="Von Schantz C" first="Carina" last="Von Schantz">Carina Von Schantz</name><affiliation wicri:level="4"><nlm:affiliation>Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki 00290, Finland.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki 00290</wicri:regionArea><orgName type="university">Université d'Helsinki</orgName><placeName><settlement type="city">Helsinki</settlement><region type="région" nuts="2">Uusimaa</region></placeName></affiliation></author><author><name sortKey="Carragher, Neil O" sort="Carragher, Neil O" uniqKey="Carragher N" first="Neil O" last="Carragher">Neil O. Carragher</name><affiliation wicri:level="4"><nlm:affiliation>Cancer Research UK Edinburgh Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XR, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Cancer Research UK Edinburgh Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XR</wicri:regionArea><orgName type="university">Université d'Édimbourg</orgName><placeName><settlement type="city">Édimbourg</settlement><region type="country">Écosse</region></placeName></affiliation></author></analytic><series><title level="j">Nature reviews. Drug discovery</title><idno type="eISSN">1474-1784</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Cell Culture Techniques (methods)</term><term>Cell Line, Transformed</term><term>Drug Discovery (methods)</term><term>Drug Evaluation, Preclinical (methods)</term><term>High-Throughput Screening Assays (methods)</term><term>Humans</term><term>Induced Pluripotent Stem Cells (drug effects)</term><term>Induced Pluripotent Stem Cells (physiology)</term><term>Models, Biological</term><term>Pharmaceutical Preparations (administration & dosage)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Cellules souches pluripotentes induites ()</term><term>Cellules souches pluripotentes induites (physiologie)</term><term>Découverte de médicament ()</term><term>Humains</term><term>Lignée de cellules transformées</term><term>Modèles biologiques</term><term>Préparations pharmaceutiques (administration et posologie)</term><term>Techniques de culture cellulaire ()</term><term>Tests de criblage à haut débit ()</term><term>Évaluation préclinique de médicament ()</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Pharmaceutical Preparations</term></keywords><keywords scheme="MESH" qualifier="administration et posologie" xml:lang="fr"><term>Préparations pharmaceutiques</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Induced Pluripotent Stem Cells</term></keywords><keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Cell Culture Techniques</term><term>Drug Discovery</term><term>Drug Evaluation, Preclinical</term><term>High-Throughput Screening Assays</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Cellules souches pluripotentes induites</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Induced Pluripotent Stem Cells</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cell Line, Transformed</term><term>Humans</term><term>Models, Biological</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Cellules souches pluripotentes induites</term><term>Découverte de médicament</term><term>Humains</term><term>Lignée de cellules transformées</term><term>Modèles biologiques</term><term>Techniques de culture cellulaire</term><term>Tests de criblage à haut débit</term><term>Évaluation préclinique de médicament</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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.</div></front></TEI></record>Pour manipuler ce document sous Unix (Dilib)
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