Rapid optimization of drug combinations for the optimal angiostatic treatment of cancer
Identifieur interne : 000D72 ( Main/Exploration ); précédent : 000D71; suivant : 000D73Rapid optimization of drug combinations for the optimal angiostatic treatment of cancer
Auteurs : Andrea Weiss [Suisse, Pays-Bas] ; Xianting Ding [République populaire de Chine] ; Judy R. Van Beijnum [Pays-Bas] ; Ieong Wong [États-Unis] ; Tse J. Wong [Pays-Bas] ; Robert H. Berndsen [Suisse, Pays-Bas] ; Olivier Dormond [Suisse] ; Marchien Dallinga [Pays-Bas] ; Li Shen [États-Unis] ; Reinier O. Schlingemann [Pays-Bas] ; Roberto Pili [États-Unis] ; Chih-Ming Ho [États-Unis] ; Paul J. Dyson [Suisse] ; Hubert Van Den Bergh [Suisse] ; Arjan W. Griffioen [Pays-Bas] ; Patrycja Nowak-Sliwinska [Suisse, Pays-Bas]Source :
- Angiogenesis [ 0969-6970 ] ; 2015.
Abstract
Drug combinations can improve angiostatic cancer treatment efficacy and enable the reduction of side effects and drug resistance. Combining drugs is non-trivial due to the high number of possibilities. We applied a feedback system control (FSC) technique with a population-based stochastic search algorithm to navigate through the large parametric space of nine angiostatic drugs at four concentrations to identify optimal low-dose drug combinations. This implied an iterative approach of in vitro testing of endothelial cell viability and algorithm-based analysis. The optimal synergistic drug combination, containing erlotinib, BEZ-235 and RAPTA-C, was reached in a small number of iterations. Final drug combinations showed enhanced endothelial cell specificity and synergistically inhibited proliferation (
The online version of this article (doi:10.1007/s10456-015-9462-9) contains supplementary material, which is available to authorized users.
Url:
DOI: 10.1007/s10456-015-9462-9
PubMed: 25824484
PubMed Central: 4473022
Affiliations:
- Pays-Bas, République populaire de Chine, Suisse, États-Unis
- Californie, Canton de Vaud, État de New York
- Lausanne
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Van Beijnum</name><affiliation wicri:level="1"><nlm:aff id="Aff2">Department of Medical Oncology, VU University Medical Center, 1007 MB Amsterdam, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Medical Oncology, VU University Medical Center, 1007 MB Amsterdam</wicri:regionArea><wicri:noRegion>1007 MB Amsterdam</wicri:noRegion></affiliation></author><author><name sortKey="Wong, Ieong" sort="Wong, Ieong" uniqKey="Wong I" first="Ieong" last="Wong">Ieong Wong</name><affiliation wicri:level="2"><nlm:aff id="Aff4">Department of Mechanical and Aerospace Engineering, University of California, Los Angeles, CA 90095 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Californie</region></placeName><wicri:cityArea>Department of Mechanical and Aerospace Engineering, University of California, Los Angeles</wicri:cityArea></affiliation></author><author><name sortKey="Wong, Tse J" sort="Wong, Tse J" uniqKey="Wong T" first="Tse J." last="Wong">Tse J. Wong</name><affiliation wicri:level="1"><nlm:aff id="Aff2">Department of Medical Oncology, VU University Medical Center, 1007 MB Amsterdam, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Medical Oncology, VU University Medical Center, 1007 MB Amsterdam</wicri:regionArea><wicri:noRegion>1007 MB Amsterdam</wicri:noRegion></affiliation></author><author><name sortKey="Berndsen, Robert H" sort="Berndsen, Robert H" uniqKey="Berndsen R" first="Robert H." last="Berndsen">Robert H. Berndsen</name><affiliation wicri:level="1"><nlm:aff id="Aff1">Institute of Chemical Sciences and Engineering, Swiss Federal Institute of Technology (EPFL), 1015 Lausanne, Switzerland</nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Institute of Chemical Sciences and Engineering, Swiss Federal Institute of Technology (EPFL), 1015 Lausanne</wicri:regionArea><placeName><settlement type="city">Lausanne</settlement><region nuts="3" type="region">Canton de Vaud</region></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff2">Department of Medical Oncology, VU University Medical Center, 1007 MB Amsterdam, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Medical Oncology, VU University Medical Center, 1007 MB Amsterdam</wicri:regionArea><wicri:noRegion>1007 MB Amsterdam</wicri:noRegion></affiliation></author><author><name sortKey="Dormond, Olivier" sort="Dormond, Olivier" uniqKey="Dormond O" first="Olivier" last="Dormond">Olivier Dormond</name><affiliation wicri:level="1"><nlm:aff id="Aff5">Department of Visceral Surgery, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland</nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Department of Visceral Surgery, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne</wicri:regionArea><placeName><settlement type="city">Lausanne</settlement><region nuts="3" type="region">Canton de Vaud</region></placeName></affiliation></author><author><name sortKey="Dallinga, Marchien" sort="Dallinga, Marchien" uniqKey="Dallinga M" first="Marchien" last="Dallinga">Marchien Dallinga</name><affiliation wicri:level="1"><nlm:aff id="Aff6">Ocular Angiogenesis Group, Departments of Ophthalmology and Cell Biology and Histology, Academic Medical Center, 1100 DD Amsterdam, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Ocular Angiogenesis Group, Departments of Ophthalmology and Cell Biology and Histology, Academic Medical Center, 1100 DD Amsterdam</wicri:regionArea><wicri:noRegion>1100 DD Amsterdam</wicri:noRegion></affiliation></author><author><name sortKey="Shen, Li" sort="Shen, Li" uniqKey="Shen L" first="Li" last="Shen">Li Shen</name><affiliation wicri:level="2"><nlm:aff id="Aff7">Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY 14263 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Department of Medicine, Roswell Park Cancer Institute, Buffalo</wicri:cityArea></affiliation></author><author><name sortKey="Schlingemann, Reinier O" sort="Schlingemann, Reinier O" uniqKey="Schlingemann R" first="Reinier O." last="Schlingemann">Reinier O. Schlingemann</name><affiliation wicri:level="1"><nlm:aff id="Aff6">Ocular Angiogenesis Group, Departments of Ophthalmology and Cell Biology and Histology, Academic Medical Center, 1100 DD Amsterdam, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Ocular Angiogenesis Group, Departments of Ophthalmology and Cell Biology and Histology, Academic Medical Center, 1100 DD Amsterdam</wicri:regionArea><wicri:noRegion>1100 DD Amsterdam</wicri:noRegion></affiliation></author><author><name sortKey="Pili, Roberto" sort="Pili, Roberto" uniqKey="Pili R" first="Roberto" last="Pili">Roberto Pili</name><affiliation wicri:level="2"><nlm:aff id="Aff7">Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY 14263 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Department of Medicine, Roswell Park Cancer Institute, Buffalo</wicri:cityArea></affiliation></author><author><name sortKey="Ho, Chih Ming" sort="Ho, Chih Ming" uniqKey="Ho C" first="Chih-Ming" last="Ho">Chih-Ming Ho</name><affiliation wicri:level="2"><nlm:aff id="Aff4">Department of Mechanical and Aerospace Engineering, University of California, Los Angeles, CA 90095 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Californie</region></placeName><wicri:cityArea>Department of Mechanical and Aerospace Engineering, University of California, Los Angeles</wicri:cityArea></affiliation></author><author><name sortKey="Dyson, Paul J" sort="Dyson, Paul J" uniqKey="Dyson P" first="Paul J." last="Dyson">Paul J. 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Van Beijnum</name><affiliation wicri:level="1"><nlm:aff id="Aff2">Department of Medical Oncology, VU University Medical Center, 1007 MB Amsterdam, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Medical Oncology, VU University Medical Center, 1007 MB Amsterdam</wicri:regionArea><wicri:noRegion>1007 MB Amsterdam</wicri:noRegion></affiliation></author><author><name sortKey="Wong, Ieong" sort="Wong, Ieong" uniqKey="Wong I" first="Ieong" last="Wong">Ieong Wong</name><affiliation wicri:level="2"><nlm:aff id="Aff4">Department of Mechanical and Aerospace Engineering, University of California, Los Angeles, CA 90095 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Californie</region></placeName><wicri:cityArea>Department of Mechanical and Aerospace Engineering, University of California, Los Angeles</wicri:cityArea></affiliation></author><author><name sortKey="Wong, Tse J" sort="Wong, Tse J" uniqKey="Wong T" first="Tse J." last="Wong">Tse J. Wong</name><affiliation wicri:level="1"><nlm:aff id="Aff2">Department of Medical Oncology, VU University Medical Center, 1007 MB Amsterdam, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Medical Oncology, VU University Medical Center, 1007 MB Amsterdam</wicri:regionArea><wicri:noRegion>1007 MB Amsterdam</wicri:noRegion></affiliation></author><author><name sortKey="Berndsen, Robert H" sort="Berndsen, Robert H" uniqKey="Berndsen R" first="Robert H." last="Berndsen">Robert H. Berndsen</name><affiliation wicri:level="1"><nlm:aff id="Aff1">Institute of Chemical Sciences and Engineering, Swiss Federal Institute of Technology (EPFL), 1015 Lausanne, Switzerland</nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Institute of Chemical Sciences and Engineering, Swiss Federal Institute of Technology (EPFL), 1015 Lausanne</wicri:regionArea><placeName><settlement type="city">Lausanne</settlement><region nuts="3" type="region">Canton de Vaud</region></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff2">Department of Medical Oncology, VU University Medical Center, 1007 MB Amsterdam, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Medical Oncology, VU University Medical Center, 1007 MB Amsterdam</wicri:regionArea><wicri:noRegion>1007 MB Amsterdam</wicri:noRegion></affiliation></author><author><name sortKey="Dormond, Olivier" sort="Dormond, Olivier" uniqKey="Dormond O" first="Olivier" last="Dormond">Olivier Dormond</name><affiliation wicri:level="1"><nlm:aff id="Aff5">Department of Visceral Surgery, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland</nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Department of Visceral Surgery, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne</wicri:regionArea><placeName><settlement type="city">Lausanne</settlement><region nuts="3" type="region">Canton de Vaud</region></placeName></affiliation></author><author><name sortKey="Dallinga, Marchien" sort="Dallinga, Marchien" uniqKey="Dallinga M" first="Marchien" last="Dallinga">Marchien Dallinga</name><affiliation wicri:level="1"><nlm:aff id="Aff6">Ocular Angiogenesis Group, Departments of Ophthalmology and Cell Biology and Histology, Academic Medical Center, 1100 DD Amsterdam, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Ocular Angiogenesis Group, Departments of Ophthalmology and Cell Biology and Histology, Academic Medical Center, 1100 DD Amsterdam</wicri:regionArea><wicri:noRegion>1100 DD Amsterdam</wicri:noRegion></affiliation></author><author><name sortKey="Shen, Li" sort="Shen, Li" uniqKey="Shen L" first="Li" last="Shen">Li Shen</name><affiliation wicri:level="2"><nlm:aff id="Aff7">Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY 14263 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Department of Medicine, Roswell Park Cancer Institute, Buffalo</wicri:cityArea></affiliation></author><author><name sortKey="Schlingemann, Reinier O" sort="Schlingemann, Reinier O" uniqKey="Schlingemann R" first="Reinier O." last="Schlingemann">Reinier O. Schlingemann</name><affiliation wicri:level="1"><nlm:aff id="Aff6">Ocular Angiogenesis Group, Departments of Ophthalmology and Cell Biology and Histology, Academic Medical Center, 1100 DD Amsterdam, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Ocular Angiogenesis Group, Departments of Ophthalmology and Cell Biology and Histology, Academic Medical Center, 1100 DD Amsterdam</wicri:regionArea><wicri:noRegion>1100 DD Amsterdam</wicri:noRegion></affiliation></author><author><name sortKey="Pili, Roberto" sort="Pili, Roberto" uniqKey="Pili R" first="Roberto" last="Pili">Roberto Pili</name><affiliation wicri:level="2"><nlm:aff id="Aff7">Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY 14263 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Department of Medicine, Roswell Park Cancer Institute, Buffalo</wicri:cityArea></affiliation></author><author><name sortKey="Ho, Chih Ming" sort="Ho, Chih Ming" uniqKey="Ho C" first="Chih-Ming" last="Ho">Chih-Ming Ho</name><affiliation wicri:level="2"><nlm:aff id="Aff4">Department of Mechanical and Aerospace Engineering, University of California, Los Angeles, CA 90095 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Californie</region></placeName><wicri:cityArea>Department of Mechanical and Aerospace Engineering, University of California, Los Angeles</wicri:cityArea></affiliation></author><author><name sortKey="Dyson, Paul J" sort="Dyson, Paul J" uniqKey="Dyson P" first="Paul J." last="Dyson">Paul J. Dyson</name><affiliation wicri:level="1"><nlm:aff id="Aff1">Institute of Chemical Sciences and Engineering, Swiss Federal Institute of Technology (EPFL), 1015 Lausanne, Switzerland</nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Institute of Chemical Sciences and Engineering, Swiss Federal Institute of Technology (EPFL), 1015 Lausanne</wicri:regionArea><placeName><settlement type="city">Lausanne</settlement><region nuts="3" type="region">Canton de Vaud</region></placeName></affiliation></author><author><name sortKey="Van Den Bergh, Hubert" sort="Van Den Bergh, Hubert" uniqKey="Van Den Bergh H" first="Hubert" last="Van Den Bergh">Hubert Van Den Bergh</name><affiliation wicri:level="1"><nlm:aff id="Aff1">Institute of Chemical Sciences and Engineering, Swiss Federal Institute of Technology (EPFL), 1015 Lausanne, Switzerland</nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Institute of Chemical Sciences and Engineering, Swiss Federal Institute of Technology (EPFL), 1015 Lausanne</wicri:regionArea><placeName><settlement type="city">Lausanne</settlement><region nuts="3" type="region">Canton de Vaud</region></placeName></affiliation></author><author><name sortKey="Griffioen, Arjan W" sort="Griffioen, Arjan W" uniqKey="Griffioen A" first="Arjan W." last="Griffioen">Arjan W. Griffioen</name><affiliation wicri:level="1"><nlm:aff id="Aff2">Department of Medical Oncology, VU University Medical Center, 1007 MB Amsterdam, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Medical Oncology, VU University Medical Center, 1007 MB Amsterdam</wicri:regionArea><wicri:noRegion>1007 MB Amsterdam</wicri:noRegion></affiliation></author><author><name sortKey="Nowak Sliwinska, Patrycja" sort="Nowak Sliwinska, Patrycja" uniqKey="Nowak Sliwinska P" first="Patrycja" last="Nowak-Sliwinska">Patrycja Nowak-Sliwinska</name><affiliation wicri:level="1"><nlm:aff id="Aff1">Institute of Chemical Sciences and Engineering, Swiss Federal Institute of Technology (EPFL), 1015 Lausanne, Switzerland</nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Institute of Chemical Sciences and Engineering, Swiss Federal Institute of Technology (EPFL), 1015 Lausanne</wicri:regionArea><placeName><settlement type="city">Lausanne</settlement><region nuts="3" type="region">Canton de Vaud</region></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff2">Department of Medical Oncology, VU University Medical Center, 1007 MB Amsterdam, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Medical Oncology, VU University Medical Center, 1007 MB Amsterdam</wicri:regionArea><wicri:noRegion>1007 MB Amsterdam</wicri:noRegion></affiliation></author></analytic><series><title level="j">Angiogenesis</title><idno type="ISSN">0969-6970</idno><idno type="eISSN">1573-7209</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Drug combinations can improve angiostatic cancer treatment efficacy and enable the reduction of side effects and drug resistance. Combining drugs is non-trivial due to the high number of possibilities. We applied a feedback system control (FSC) technique with a population-based stochastic search algorithm to navigate through the large parametric space of nine angiostatic drugs at four concentrations to identify optimal low-dose drug combinations. This implied an iterative approach of in vitro testing of endothelial cell viability and algorithm-based analysis. The optimal synergistic drug combination, containing erlotinib, BEZ-235 and RAPTA-C, was reached in a small number of iterations. Final drug combinations showed enhanced endothelial cell specificity and synergistically inhibited proliferation (<italic>p</italic> < 0.001), but not migration of endothelial cells, and forced enhanced numbers of endothelial cells to undergo apoptosis (<italic>p</italic> < 0.01). Successful translation of this drug combination was achieved in two preclinical in vivo tumor models. Tumor growth was inhibited synergistically and significantly (<italic>p</italic> < 0.05 and <italic>p</italic> < 0.01, respectively) using reduced drug doses as compared to optimal single-drug concentrations. At the applied conditions, single-drug monotherapies had no or negligible activity in these models. We suggest that FSC can be used for rapid identification of effective, reduced dose, multi-drug combinations for the treatment of cancer and other diseases.</p><sec><title>Electronic supplementary material</title><p>The online version of this article (doi:10.1007/s10456-015-9462-9) contains supplementary material, which is available to authorized users.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Folkman, J" uniqKey="Folkman J">J Folkman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Carmeliet, P" uniqKey="Carmeliet P">P Carmeliet</name></author><author><name sortKey="Jain, Rk" uniqKey="Jain R">RK Jain</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gonzalez Angulo, Am" uniqKey="Gonzalez Angulo A">AM Gonzalez-Angulo</name></author><author><name sortKey="Hortobagyi, Gn" uniqKey="Hortobagyi G">GN Hortobagyi</name></author><author><name sortKey="Ellis, 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Nowak-Sliwinska</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Pays-Bas</li><li>République populaire de Chine</li><li>Suisse</li><li>États-Unis</li></country><region><li>Californie</li><li>Canton de Vaud</li><li>État de New York</li></region><settlement><li>Lausanne</li></settlement></list><tree><country name="Suisse"><region name="Canton de Vaud"><name sortKey="Weiss, Andrea" sort="Weiss, Andrea" uniqKey="Weiss A" first="Andrea" last="Weiss">Andrea Weiss</name></region><name sortKey="Berndsen, Robert H" sort="Berndsen, Robert H" uniqKey="Berndsen R" first="Robert H." last="Berndsen">Robert H. 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Berndsen</name><name sortKey="Dallinga, Marchien" sort="Dallinga, Marchien" uniqKey="Dallinga M" first="Marchien" last="Dallinga">Marchien Dallinga</name><name sortKey="Griffioen, Arjan W" sort="Griffioen, Arjan W" uniqKey="Griffioen A" first="Arjan W." last="Griffioen">Arjan W. Griffioen</name><name sortKey="Nowak Sliwinska, Patrycja" sort="Nowak Sliwinska, Patrycja" uniqKey="Nowak Sliwinska P" first="Patrycja" last="Nowak-Sliwinska">Patrycja Nowak-Sliwinska</name><name sortKey="Schlingemann, Reinier O" sort="Schlingemann, Reinier O" uniqKey="Schlingemann R" first="Reinier O." last="Schlingemann">Reinier O. Schlingemann</name><name sortKey="Van Beijnum, Judy R" sort="Van Beijnum, Judy R" uniqKey="Van Beijnum J" first="Judy R." last="Van Beijnum">Judy R. Van Beijnum</name><name sortKey="Wong, Tse J" sort="Wong, Tse J" uniqKey="Wong T" first="Tse J." last="Wong">Tse J. Wong</name></country><country name="République populaire de Chine"><noRegion><name sortKey="Ding, Xianting" sort="Ding, Xianting" uniqKey="Ding X" first="Xianting" last="Ding">Xianting Ding</name></noRegion></country><country name="États-Unis"><region name="Californie"><name sortKey="Wong, Ieong" sort="Wong, Ieong" uniqKey="Wong I" first="Ieong" last="Wong">Ieong Wong</name></region><name sortKey="Ho, Chih Ming" sort="Ho, Chih Ming" uniqKey="Ho C" first="Chih-Ming" last="Ho">Chih-Ming Ho</name><name sortKey="Pili, Roberto" sort="Pili, Roberto" uniqKey="Pili R" first="Roberto" last="Pili">Roberto Pili</name><name sortKey="Shen, Li" sort="Shen, Li" uniqKey="Shen L" first="Li" last="Shen">Li Shen</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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