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A simplified interventional mapping system (SIMS) for the selection of combinations of targeted treatments in non-small cell lung cancer
Non-small cell lung cancer (NSCLC) is a leading cause of death worldwide. Targeted monotherapies produce high regression rates, albeit for limited patient subgroups, who inevitably succumb. We present a novel strategy for identifying customized combinations of triplets of targeted agents, utilizing...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
Impact Journals LLC
2015
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4546456/ https://www.ncbi.nlm.nih.gov/pubmed/25944621 |
| _version_ | 1782386933115125760 |
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| author | Lazar, Vladimir Rubin, Eitan Depil, Stephane Pawitan, Yudi Martini, Jean-François Gomez-Navarro, Jesus Yver, Antoine Kan, Zhengyin Dry, Jonathan R. Kehren, Jeanne Validire, Pierre Rodon, Jordi Vielh, Philippe Ducreux, Michel Galbraith, Susan Lehnert, Manfred Onn, Amir Berger, Raanan Pierotti, Marco A. Porgador, Angel Pramesh, CS Ye, Ding-wei Carvalho, Andre L. Batist, Gerald Le Chevalier, Thierry Morice, Philippe Besse, Benjamin Vassal, Gilles Mortlock, Andrew Hansson, Johan Berindan-Neagoe, Ioana Dann, Robert Haspel, Joel Irimie, Alexandru Laderman, Steve Nechushtan, Hovav Al Omari, Amal S. Haywood, Trent Bresson, Catherine Soo, Khee Chee Osman, Iman Mata, Hilario Lee, Jack J. Jhaveri, Komal Meurice, Guillaume Palmer, Gary Lacroix, Ludovic Koscielny, Serge Eterovic, Karina Agda Blay, Jean-Yves Buller, Richard Eggermont, Alexander Schilsky, Richard L. Mendelsohn, John Soria, Jean-Charles Rothenberg, Mace Scoazec, Jean-Yves Ki Hong, Waun Kurzrock, Razelle |
| author_facet | Lazar, Vladimir Rubin, Eitan Depil, Stephane Pawitan, Yudi Martini, Jean-François Gomez-Navarro, Jesus Yver, Antoine Kan, Zhengyin Dry, Jonathan R. Kehren, Jeanne Validire, Pierre Rodon, Jordi Vielh, Philippe Ducreux, Michel Galbraith, Susan Lehnert, Manfred Onn, Amir Berger, Raanan Pierotti, Marco A. Porgador, Angel Pramesh, CS Ye, Ding-wei Carvalho, Andre L. Batist, Gerald Le Chevalier, Thierry Morice, Philippe Besse, Benjamin Vassal, Gilles Mortlock, Andrew Hansson, Johan Berindan-Neagoe, Ioana Dann, Robert Haspel, Joel Irimie, Alexandru Laderman, Steve Nechushtan, Hovav Al Omari, Amal S. Haywood, Trent Bresson, Catherine Soo, Khee Chee Osman, Iman Mata, Hilario Lee, Jack J. Jhaveri, Komal Meurice, Guillaume Palmer, Gary Lacroix, Ludovic Koscielny, Serge Eterovic, Karina Agda Blay, Jean-Yves Buller, Richard Eggermont, Alexander Schilsky, Richard L. Mendelsohn, John Soria, Jean-Charles Rothenberg, Mace Scoazec, Jean-Yves Ki Hong, Waun Kurzrock, Razelle |
| author_sort | Lazar, Vladimir |
| collection | PubMed |
| description | Non-small cell lung cancer (NSCLC) is a leading cause of death worldwide. Targeted monotherapies produce high regression rates, albeit for limited patient subgroups, who inevitably succumb. We present a novel strategy for identifying customized combinations of triplets of targeted agents, utilizing a simplified interventional mapping system (SIMS) that merges knowledge about existent drugs and their impact on the hallmarks of cancer. Based on interrogation of matched lung tumor and normal tissue using targeted genomic sequencing, copy number variation, transcriptomics, and miRNA expression, the activation status of 24 interventional nodes was elucidated. An algorithm was developed to create a scoring system that enables ranking of the activated interventional nodes for each patient. Based on the trends of co-activation at interventional points, combinations of drug triplets were defined in order to overcome resistance. This methodology will inform a prospective trial to be conducted by the WIN consortium, aiming to significantly impact survival in metastatic NSCLC and other malignancies. |
| format | Online Article Text |
| id | pubmed-4546456 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2015 |
| publisher | Impact Journals LLC |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-45464562015-08-27 A simplified interventional mapping system (SIMS) for the selection of combinations of targeted treatments in non-small cell lung cancer Lazar, Vladimir Rubin, Eitan Depil, Stephane Pawitan, Yudi Martini, Jean-François Gomez-Navarro, Jesus Yver, Antoine Kan, Zhengyin Dry, Jonathan R. Kehren, Jeanne Validire, Pierre Rodon, Jordi Vielh, Philippe Ducreux, Michel Galbraith, Susan Lehnert, Manfred Onn, Amir Berger, Raanan Pierotti, Marco A. Porgador, Angel Pramesh, CS Ye, Ding-wei Carvalho, Andre L. Batist, Gerald Le Chevalier, Thierry Morice, Philippe Besse, Benjamin Vassal, Gilles Mortlock, Andrew Hansson, Johan Berindan-Neagoe, Ioana Dann, Robert Haspel, Joel Irimie, Alexandru Laderman, Steve Nechushtan, Hovav Al Omari, Amal S. Haywood, Trent Bresson, Catherine Soo, Khee Chee Osman, Iman Mata, Hilario Lee, Jack J. Jhaveri, Komal Meurice, Guillaume Palmer, Gary Lacroix, Ludovic Koscielny, Serge Eterovic, Karina Agda Blay, Jean-Yves Buller, Richard Eggermont, Alexander Schilsky, Richard L. Mendelsohn, John Soria, Jean-Charles Rothenberg, Mace Scoazec, Jean-Yves Ki Hong, Waun Kurzrock, Razelle Oncotarget Research Paper Non-small cell lung cancer (NSCLC) is a leading cause of death worldwide. Targeted monotherapies produce high regression rates, albeit for limited patient subgroups, who inevitably succumb. We present a novel strategy for identifying customized combinations of triplets of targeted agents, utilizing a simplified interventional mapping system (SIMS) that merges knowledge about existent drugs and their impact on the hallmarks of cancer. Based on interrogation of matched lung tumor and normal tissue using targeted genomic sequencing, copy number variation, transcriptomics, and miRNA expression, the activation status of 24 interventional nodes was elucidated. An algorithm was developed to create a scoring system that enables ranking of the activated interventional nodes for each patient. Based on the trends of co-activation at interventional points, combinations of drug triplets were defined in order to overcome resistance. This methodology will inform a prospective trial to be conducted by the WIN consortium, aiming to significantly impact survival in metastatic NSCLC and other malignancies. Impact Journals LLC 2015-04-03 /pmc/articles/PMC4546456/ /pubmed/25944621 Text en Copyright: © 2015 Lazar et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| spellingShingle | Research Paper Lazar, Vladimir Rubin, Eitan Depil, Stephane Pawitan, Yudi Martini, Jean-François Gomez-Navarro, Jesus Yver, Antoine Kan, Zhengyin Dry, Jonathan R. Kehren, Jeanne Validire, Pierre Rodon, Jordi Vielh, Philippe Ducreux, Michel Galbraith, Susan Lehnert, Manfred Onn, Amir Berger, Raanan Pierotti, Marco A. Porgador, Angel Pramesh, CS Ye, Ding-wei Carvalho, Andre L. Batist, Gerald Le Chevalier, Thierry Morice, Philippe Besse, Benjamin Vassal, Gilles Mortlock, Andrew Hansson, Johan Berindan-Neagoe, Ioana Dann, Robert Haspel, Joel Irimie, Alexandru Laderman, Steve Nechushtan, Hovav Al Omari, Amal S. Haywood, Trent Bresson, Catherine Soo, Khee Chee Osman, Iman Mata, Hilario Lee, Jack J. Jhaveri, Komal Meurice, Guillaume Palmer, Gary Lacroix, Ludovic Koscielny, Serge Eterovic, Karina Agda Blay, Jean-Yves Buller, Richard Eggermont, Alexander Schilsky, Richard L. Mendelsohn, John Soria, Jean-Charles Rothenberg, Mace Scoazec, Jean-Yves Ki Hong, Waun Kurzrock, Razelle A simplified interventional mapping system (SIMS) for the selection of combinations of targeted treatments in non-small cell lung cancer |
| title | A simplified interventional mapping system (SIMS) for the selection of combinations of targeted treatments in non-small cell lung cancer |
| title_full | A simplified interventional mapping system (SIMS) for the selection of combinations of targeted treatments in non-small cell lung cancer |
| title_fullStr | A simplified interventional mapping system (SIMS) for the selection of combinations of targeted treatments in non-small cell lung cancer |
| title_full_unstemmed | A simplified interventional mapping system (SIMS) for the selection of combinations of targeted treatments in non-small cell lung cancer |
| title_short | A simplified interventional mapping system (SIMS) for the selection of combinations of targeted treatments in non-small cell lung cancer |
| title_sort | simplified interventional mapping system (sims) for the selection of combinations of targeted treatments in non-small cell lung cancer |
| topic | Research Paper |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4546456/ https://www.ncbi.nlm.nih.gov/pubmed/25944621 |
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