Web of Science: 18 cites, Scopus: 19 cites, Google Scholar: cites,
A simplified interventional mapping system (SIMS) for the selection of combinations of targeted treatments in non-small cell lung cancer
Lazar, Vladimir (Gustave-Roussy Cancer Center (France))
Rubin, Eitan (Ben-Gurion University of the Negev (Israel))
Depil, Stephane (Leon Berard Cancer Center (France))
Pawitan, Yudi (Karolinska Institutet (Estocolm, Suècia))
Martini, Jean-François (Pfizer Oncology Research (USA))
Gomez-Navarro, Jesus (Takeda Pharmaceuticals International Co.(USA))
Yver, Antoine (AstraZeneca Pharmaceuticals LP (USA))
Kan, Zhengyin (Pfizer Oncology Research (USA))
Dry, Jonathan R. (AstraZeneca Pharmaceuticals LP (USA))
Kehren, Jeanne (Sanofi (France))
Validire, Pierre (Institut Mutualiste Montsouris (France))
Rodón Ahnert, Jordi (Vall d'Hebron Institut d'Oncologia)
Vielh, Philippe (Gustave-Roussy Cancer Center (France))
Ducreux, Michel (Gustave-Roussy Cancer Center (France))
Galbraith, Susan (AstraZeneca Pharmaceuticals LP (USA))
Lehnert, Manfred (Takeda Pharmaceuticals International Co. (USA))
Onn, Amir (Chaim Sheba Medical Center (Israel))
Berger, Raanan (Chaim Sheba Medical Center (Israel))
Pierotti, Marco A. (Fondazione IRCCS Istituto Nazionale dei Tumori (Italy))
Porgador, Angel (Ben-Gurion University of the Negev (Israel))
Pramesh, CS (Tata Memorial Centre (India))
Ye, Ding-wei (Fudan University Shanghai Cancer Center (China))
Carvalho, Andre L. (Barretos Cancer Hospital. Fundacao Pio XII (Brazil))
Batist, Gerald (Jewish General Hospita. Segal Cancer Centre (Canada))
Le Chevalier, Thierry (Gustave-Roussy Cancer Center (France))
Morice, Philippe (Gustave-Roussy Cancer Center (France))
Besse, Benjamin (Gustave-Roussy Cancer Center (France))
Vassal, Gilles (Gustave-Roussy Cancer Center (France))
Mortlock, Andrew (AstraZeneca Pharmaceuticals LP (USA))
Hansson, Johan (Karolinska Institutet (Estocolm, Suècia))
Berindan-Neagoe, Ioana (Universitatea de Medicină şi Farmacie Iuliu Haţieganu Cluj-Napoca (Romania))
Dann, Robert (General Electric Healthcare (USA))
Haspel, Joel (Oracle Corporation (UK))
Irimie, Alexandru (Universitatea de Medicină şi Farmacie Iuliu Haţieganu Cluj-Napoca (Romania))
Laderman, Steve (Agilent Technologies (USA))
Nechushtan, Hovav (Hadassah Hebrew University Medical Center (Israel))
Al Omari, Amal S. (King Hussein Cancer Center (Jordan))
Haywood, Trent (Blue Cross Blue Shield Association (USA))
Bresson, Catherine (WIN Consortium (France))
Soo, Khee Chee (National Cancer Centre (Singapore))
Osman, Iman (New York University Langone Medical Center (USA))
Mata, Hilario (MD Anderson Cancer Center (USA))
Lee, Jack J. (MD Anderson Cancer Center (USA))
Jhaveri, Komal (New York University Langone Medical Center (USA))
Meurice, Guillaume (Gustave-Roussy Cancer Center (France))
Palmer, Gary (Foundation Medicine Inc. (USA))
Lacroix, Ludovic (Gustave-Roussy Cancer Center (France))
Koscielny, Serge (Gustave-Roussy Cancer Center (France))
Eterovic, Karina Agda (MD Anderson Cancer Center (USA))
Blay, Jean-Yves (Leon Berard Cancer Center (France))
Buller, Richard (Pfizer Oncology Research (USA))
Eggermont, Alexander (Gustave-Roussy Cancer Center (France))
Schilsky, Richard L. (American Society of Clinical Oncology (USA))
Mendelsohn, John (MD Anderson Cancer Center (USA))
Soria, Jean-Charles (Gustave-Roussy Cancer Center (France))
Rothenberg, Mace (Pfizer Oncology Research (USA))
Scoazec, Jean-Yves (Gustave-Roussy Cancer Center (France))
Ki Hong, Waun (MD Anderson Cancer Center (USA))
Kurzrock, Razelle (Moores Cancer Center (USA))
Universitat Autònoma de Barcelona

Data: 2015
Resum: 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.
Ajuts: European Commission 306125
European Commission 037665
Drets: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. Creative Commons
Llengua: Anglès
Document: Article ; recerca ; Versió publicada
Matèria: Tri-therapy ; NSCLC ; Targeted therapies ; Algorithm ; Pathway
Publicat a: Oncotarget, Vol. 6, no. 16 (June 2015) , p. 14139-14152, ISSN 1949-2553

DOI: 10.18632/oncotarget.3741
PMID: 25944621

14 p, 4.6 MB

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