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Screening out irrelevant cell-based models of disease.

Identifieur interne : 003B24 ( Ncbi/Merge ); précédent : 003B23; suivant : 003B25

Screening 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 :

RBID : pubmed:27616293

Descripteurs français

English descriptors

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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Le document en format XML

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<name sortKey="Price, Leo S" sort="Price, Leo S" uniqKey="Price L" first="Leo S" last="Price">Leo S. Price</name>
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<country xml:lang="fr">Pays-Bas</country>
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<name sortKey="Von Schantz, Carina" sort="Von Schantz, Carina" uniqKey="Von Schantz C" first="Carina" last="Von Schantz">Carina Von Schantz</name>
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<nlm:affiliation>Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki 00290, Finland.</nlm:affiliation>
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<orgName type="university">Université d'Helsinki</orgName>
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<name sortKey="Carragher, Neil O" sort="Carragher, Neil O" uniqKey="Carragher N" first="Neil O" last="Carragher">Neil O. Carragher</name>
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<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>
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<settlement type="city">Édimbourg</settlement>
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<title level="j">Nature reviews. Drug discovery</title>
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<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>
<pubmed>
<MedlineCitation Status="MEDLINE" Owner="NLM">
<PMID Version="1">27616293</PMID>
<DateCreated>
<Year>2016</Year>
<Month>09</Month>
<Day>12</Day>
</DateCreated>
<DateCompleted>
<Year>2017</Year>
<Month>02</Month>
<Day>15</Day>
</DateCompleted>
<DateRevised>
<Year>2017</Year>
<Month>08</Month>
<Day>17</Day>
</DateRevised>
<Article PubModel="Print-Electronic">
<Journal>
<ISSN IssnType="Electronic">1474-1784</ISSN>
<JournalIssue CitedMedium="Internet">
<Volume>15</Volume>
<Issue>11</Issue>
<PubDate>
<Year>2016</Year>
<Month>11</Month>
</PubDate>
</JournalIssue>
<Title>Nature reviews. Drug discovery</Title>
<ISOAbbreviation>Nat Rev Drug Discov</ISOAbbreviation>
</Journal>
<ArticleTitle>Screening out irrelevant cell-based models of disease.</ArticleTitle>
<Pagination>
<MedlinePgn>751-769</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1038/nrd.2016.175</ELocationID>
<Abstract>
<AbstractText>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.</AbstractText>
</Abstract>
<AuthorList CompleteYN="Y">
<Author ValidYN="Y">
<LastName>Horvath</LastName>
<ForeName>Peter</ForeName>
<Initials>P</Initials>
<AffiliationInfo>
<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.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>European Cell-Based Assays Interest Group.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Aulner</LastName>
<ForeName>Nathalie</ForeName>
<Initials>N</Initials>
<AffiliationInfo>
<Affiliation>Imagopole-Citech, Institut Pasteur, Paris 75015, France.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>European Cell-Based Assays Interest Group.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Bickle</LastName>
<ForeName>Marc</ForeName>
<Initials>M</Initials>
<AffiliationInfo>
<Affiliation>Technology Development Studio, Max Planck Institute of Molecular Cell Biology and Genetics, Dresden 01307, Germany.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>European Cell-Based Assays Interest Group.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Davies</LastName>
<ForeName>Anthony M</ForeName>
<Initials>AM</Initials>
<AffiliationInfo>
<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.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>European Cell-Based Assays Interest Group.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Nery</LastName>
<ForeName>Elaine Del</ForeName>
<Initials>ED</Initials>
<AffiliationInfo>
<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.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>European Cell-Based Assays Interest Group.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Ebner</LastName>
<ForeName>Daniel</ForeName>
<Initials>D</Initials>
<AffiliationInfo>
<Affiliation>Target Discovery Institute, University of Oxford, Oxford OX3 7FZ, UK.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>European Cell-Based Assays Interest Group.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Montoya</LastName>
<ForeName>Maria C</ForeName>
<Initials>MC</Initials>
<AffiliationInfo>
<Affiliation>Cellomics Unit, Cell Biology &Physiology Program, Cell &Developmental Biology Area, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid 28029, Spain.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>European Cell-Based Assays Interest Group.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Östling</LastName>
<ForeName>Päivi</ForeName>
<Initials>P</Initials>
<AffiliationInfo>
<Affiliation>Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki 00290, Finland.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>Science for Life Laboratory, Department of Oncology and Pathology, Karolinska Institutet, Stockholm 17165, Sweden.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>European Cell-Based Assays Interest Group.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Pietiäinen</LastName>
<ForeName>Vilja</ForeName>
<Initials>V</Initials>
<AffiliationInfo>
<Affiliation>Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki 00290, Finland.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>European Cell-Based Assays Interest Group.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Price</LastName>
<ForeName>Leo S</ForeName>
<Initials>LS</Initials>
<AffiliationInfo>
<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.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>European Cell-Based Assays Interest Group.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Shorte</LastName>
<ForeName>Spencer L</ForeName>
<Initials>SL</Initials>
<AffiliationInfo>
<Affiliation>Imagopole-Citech, Institut Pasteur, Paris 75015, France.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>European Cell-Based Assays Interest Group.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Turcatti</LastName>
<ForeName>Gerardo</ForeName>
<Initials>G</Initials>
<AffiliationInfo>
<Affiliation>Biomolecular Screening Facility, Swiss Federal Institute of Technology (EPFL), Lausanne CH-1015, Switzerland.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>European Cell-Based Assays Interest Group.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>von Schantz</LastName>
<ForeName>Carina</ForeName>
<Initials>C</Initials>
<AffiliationInfo>
<Affiliation>Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki 00290, Finland.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>European Cell-Based Assays Interest Group.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Carragher</LastName>
<ForeName>Neil O</ForeName>
<Initials>NO</Initials>
<AffiliationInfo>
<Affiliation>Cancer Research UK Edinburgh Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XR, UK.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>European Cell-Based Assays Interest Group.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<PublicationTypeList>
<PublicationType UI="D016454">Review</PublicationType>
</PublicationTypeList>
<ArticleDate DateType="Electronic">
<Year>2016</Year>
<Month>09</Month>
<Day>12</Day>
</ArticleDate>
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<MedlineJournalInfo>
<Country>England</Country>
<MedlineTA>Nat Rev Drug Discov</MedlineTA>
<NlmUniqueID>101124171</NlmUniqueID>
<ISSNLinking>1474-1776</ISSNLinking>
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<Chemical>
<RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D004364">Pharmaceutical Preparations</NameOfSubstance>
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