Interferons at age 50: past, current and future impact on biomedicine
Identifieur interne : 003B23 ( Main/Merge ); précédent : 003B22; suivant : 003B24Interferons at age 50: past, current and future impact on biomedicine
Auteurs : Ernest C. Borden [États-Unis] ; Ganes C. Sen [États-Unis] ; Gilles Uze [France] ; Robert H. Silverman [États-Unis] ; Richard M. Ransohoff [États-Unis] ; Graham R. Foster [Royaume-Uni] ; George R. Stark [États-Unis]Source :
- Nature Reviews Drug Discovery [ 1474-1776 ] ; 2007-12.
Abstract
The family of interferon (IFN) proteins has now more than reached the potential envisioned by early discovering virologists: IFNs are not only antivirals with a spectrum of clinical effectiveness against both RNA and DNA viruses, but are also the prototypic biological response modifiers for oncology, and show effectiveness in suppressing manifestations of multiple sclerosis. Studies of IFNs have resulted in fundamental insights into cellular signalling mechanisms, gene transcription and innate and acquired immunity. Further elucidation of the multitude of IFN-induced genes, as well as drug development strategies targeting IFN production via the activation of the Toll-like receptors (TLRs), will almost certainly lead to newer and more efficacious therapeutics. Our goal is to offer a molecular and clinical perspective that will enable IFNs or their TLR agonist inducers to reach their full clinical potential.
Url:
- https://api.istex.fr/ark:/67375/GT4-KRH340F0-4/fulltext.pdf
- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7097588
DOI: 10.1038/nrd2422
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Borden</name><affiliation wicri:level="1"><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Taussig Cancer Center, Case Comprehensive Cancer Center, Mellen Center for Multiple Sclerosis, and Lerner Research Institute, The Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195</wicri:regionArea><wicri:noRegion>Ohio 44195</wicri:noRegion></affiliation><affiliation></affiliation></author><author><name sortKey="Sen, Ganes C" sort="Sen, Ganes C" uniqKey="Sen G" first="Ganes C." last="Sen">Ganes C. Sen</name><affiliation wicri:level="1"><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Taussig Cancer Center, Case Comprehensive Cancer Center, Mellen Center for Multiple Sclerosis, and Lerner Research Institute, The Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195</wicri:regionArea><wicri:noRegion>Ohio 44195</wicri:noRegion></affiliation></author><author><name sortKey="Uze, Gilles" sort="Uze, Gilles" uniqKey="Uze G" first="Gilles" last="Uze">Gilles Uze</name><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>CNRS UMR 5235, Place Eugene Bataillon, Montpellier, Cedex 5 FR34095</wicri:regionArea><placeName><region type="region" nuts="2">Occitanie (région administrative)</region><region type="old region" nuts="2">Languedoc-Roussillon</region></placeName></affiliation></author><author><name sortKey="Silverman, Robert H" sort="Silverman, Robert H" uniqKey="Silverman R" first="Robert H." last="Silverman">Robert H. Silverman</name><affiliation wicri:level="1"><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Taussig Cancer Center, Case Comprehensive Cancer Center, Mellen Center for Multiple Sclerosis, and Lerner Research Institute, The Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195</wicri:regionArea><wicri:noRegion>Ohio 44195</wicri:noRegion></affiliation></author><author><name sortKey="Ransohoff, Richard M" sort="Ransohoff, Richard M" uniqKey="Ransohoff R" first="Richard M." last="Ransohoff">Richard M. Ransohoff</name><affiliation wicri:level="1"><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Taussig Cancer Center, Case Comprehensive Cancer Center, Mellen Center for Multiple Sclerosis, and Lerner Research Institute, The Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195</wicri:regionArea><wicri:noRegion>Ohio 44195</wicri:noRegion></affiliation></author><author><name sortKey="Foster, Graham R" sort="Foster, Graham R" uniqKey="Foster G" first="Graham R." last="Foster">Graham R. Foster</name><affiliation wicri:level="1"><country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country><wicri:regionArea>Institute of Cell and Molecular Science, Queen Mary's School of Medicine, 4 Newark Street, London E1 4AT</wicri:regionArea><wicri:noRegion>London E1 4AT</wicri:noRegion></affiliation></author><author><name sortKey="Stark, George R" sort="Stark, George R" uniqKey="Stark G" first="George R." last="Stark">George R. Stark</name><affiliation wicri:level="1"><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Taussig Cancer Center, Case Comprehensive Cancer Center, Mellen Center for Multiple Sclerosis, and Lerner Research Institute, The Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195</wicri:regionArea><wicri:noRegion>Ohio 44195</wicri:noRegion></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">Nature Reviews Drug Discovery</title><idno type="ISSN">1474-1776</idno><idno type="eISSN">1474-1784</idno><imprint><publisher>Nature Publishing Group</publisher><date when="2007-12">2007-12</date><biblScope unit="vol">6</biblScope><biblScope unit="issue">12</biblScope><biblScope unit="page" from="975">975</biblScope><biblScope unit="page" to="990">990</biblScope><date type="Copyright" when="2007">2007</date></imprint><idno type="ISSN">1474-1776</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">1474-1776</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="eng">The family of interferon (IFN) proteins has now more than reached the potential envisioned by early discovering virologists: IFNs are not only antivirals with a spectrum of clinical effectiveness against both RNA and DNA viruses, but are also the prototypic biological response modifiers for oncology, and show effectiveness in suppressing manifestations of multiple sclerosis. Studies of IFNs have resulted in fundamental insights into cellular signalling mechanisms, gene transcription and innate and acquired immunity. Further elucidation of the multitude of IFN-induced genes, as well as drug development strategies targeting IFN production via the activation of the Toll-like receptors (TLRs), will almost certainly lead to newer and more efficacious therapeutics. Our goal is to offer a molecular and clinical perspective that will enable IFNs or their TLR agonist inducers to reach their full clinical potential.</div></front></TEI></ISTEX><PMC><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Interferons at age 50: past, current and future impact on biomedicine</title><author><name sortKey="Borden, Ernest C" sort="Borden, Ernest C" uniqKey="Borden E" first="Ernest C." last="Borden">Ernest C. 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Borden</name><affiliation><nlm:aff id="Aff1">Taussig Cancer Center, Case Comprehensive Cancer Center, Mellen Center for Multiple Sclerosis, and Lerner Research Institute, The Cleveland Clinic, 9500 Euclid Avenue, Cleveland, 44195 Ohio USA</nlm:aff><wicri:noCountry code="subfield">44195 Ohio USA</wicri:noCountry></affiliation></author><author><name sortKey="Sen, Ganes C" sort="Sen, Ganes C" uniqKey="Sen G" first="Ganes C." last="Sen">Ganes C. Sen</name><affiliation><nlm:aff id="Aff1">Taussig Cancer Center, Case Comprehensive Cancer Center, Mellen Center for Multiple Sclerosis, and Lerner Research Institute, The Cleveland Clinic, 9500 Euclid Avenue, Cleveland, 44195 Ohio USA</nlm:aff><wicri:noCountry code="subfield">44195 Ohio USA</wicri:noCountry></affiliation></author><author><name sortKey="Uze, Gilles" sort="Uze, Gilles" uniqKey="Uze G" first="Gilles" last="Uze">Gilles Uze</name><affiliation><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="GRID">grid.464150.2</institution-id><institution-id institution-id-type="ISNI">0000 0004 0383 9805</institution-id><institution>CNRS UMR 5235, Place Eugene Bataillon,</institution></institution-wrap>Montpellier, Cedex 5 FR34095 France</nlm:aff><wicri:noCountry code="subfield">Cedex 5 FR34095 France</wicri:noCountry></affiliation></author><author><name sortKey="Silverman, Robert H" sort="Silverman, Robert H" uniqKey="Silverman R" first="Robert H." last="Silverman">Robert H. Silverman</name><affiliation><nlm:aff id="Aff1">Taussig Cancer Center, Case Comprehensive Cancer Center, Mellen Center for Multiple Sclerosis, and Lerner Research Institute, The Cleveland Clinic, 9500 Euclid Avenue, Cleveland, 44195 Ohio USA</nlm:aff><wicri:noCountry code="subfield">44195 Ohio USA</wicri:noCountry></affiliation></author><author><name sortKey="Ransohoff, Richard M" sort="Ransohoff, Richard M" uniqKey="Ransohoff R" first="Richard M." last="Ransohoff">Richard M. Ransohoff</name><affiliation><nlm:aff id="Aff1">Taussig Cancer Center, Case Comprehensive Cancer Center, Mellen Center for Multiple Sclerosis, and Lerner Research Institute, The Cleveland Clinic, 9500 Euclid Avenue, Cleveland, 44195 Ohio USA</nlm:aff><wicri:noCountry code="subfield">44195 Ohio USA</wicri:noCountry></affiliation></author><author><name sortKey="Foster, Graham R" sort="Foster, Graham R" uniqKey="Foster G" first="Graham R." last="Foster">Graham R. Foster</name><affiliation><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="GRID">grid.4868.2</institution-id><institution-id institution-id-type="ISNI">0000 0001 2171 1133</institution-id><institution>Institute of Cell and Molecular Science, Queen Mary's School of Medicine,</institution></institution-wrap>4 Newark Street, London, E1 4AT UK</nlm:aff><wicri:noCountry code="subfield">E1 4AT UK</wicri:noCountry></affiliation></author><author><name sortKey="Stark, George R" sort="Stark, George R" uniqKey="Stark G" first="George R." last="Stark">George R. Stark</name><affiliation><nlm:aff id="Aff1">Taussig Cancer Center, Case Comprehensive Cancer Center, Mellen Center for Multiple Sclerosis, and Lerner Research Institute, The Cleveland Clinic, 9500 Euclid Avenue, Cleveland, 44195 Ohio USA</nlm:aff><wicri:noCountry code="subfield">44195 Ohio USA</wicri:noCountry></affiliation></author></analytic><series><title level="j">Nature Reviews. Drug Discovery</title><idno type="ISSN">1474-1776</idno><idno type="eISSN">1474-1784</idno><imprint><date when="2007">2007</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>Key Points</title><p id="Par8"><list list-type="bullet"><list-item><p id="Par9">On the 50th anniversary of the discovery of interferon (IFN), we offer a perspective from more than 100,000 published papers, highlighting initial pivotal discoveries and more recent findings of conceptual importance. This covers the mechanisms of IFN induction, the cellular actions of IFN and IFN-stimulated genes (ISGs), and human therapeutic applications.</p></list-item><list-item><p id="Par10">The synthesis of IFNs requires stimulation by viruses or microbial products binding to Toll-like receptors, or chemical inducers. The development of small-molecule modulators is still in its infancy, but the delineation of the responsible signalling pathways has identified many target proteins.</p></list-item><list-item><p id="Par11">IFNs constitute a large protein family that can be subdivided into three types, binding to different receptors. These receptors initiate signalling by activating a complex signalling cascade regulated at many levels, resulting in a diverse pattern of ISG induction.</p></list-item><list-item><p id="Par12">ISGs are a diverse group of more than 300 genes, which can have direct antiviral and antitumour functions. These are attractive targets for high-throughput screening for the identification of new modulators of the IFN system.</p></list-item><list-item><p id="Par13">IFNs were initially investigated for their potential as antivirals, and are now commonly used in anti-HBV (hepatitis B virus) and anti-HCV (hepatitis C virus) therapy. They might also have prophylactic or therapeutic effectiveness in SARS (severe acute respiratory syndrome), influenza or another virus pandemic.</p></list-item><list-item><p id="Par14">The first FDA approval of an IFN was, however, not for virus infection but for cancer. The mechanisms of antitumour action are incompletely understood. Aberrations of the IFN system are also emerging as important contributors to cancer development.</p></list-item><list-item><p id="Par15">IFNs also proved effectiveness in relapsing, remitting multiple sclerosis. It is now common practice to initiate IFN-β treatment at the time of diagnosis.</p></list-item><list-item><p id="Par16">Because of the effectiveness of IFNs in limiting virus replication, reducing tumour cell mass, controlling disease symptoms and prolonging survival, market sales of IFNs approach US$4 billion. 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