0 citations0 references

A simplified interventional mapping system (SIMS) for the selection of combinations of targeted treatments in non-small cell lung cancer

Oncotarget2015Vol. 6(16), pp. 14139–14152

Citations Over TimeTop 23% of 2015 papers

Vladimir Lazar, Eitan Rubin, Stéphane Depil, Yudi Pawitan, Jean‐François Martini, Jesús Gómez-Navarro, Antoine Yver, Zhengyin Kan, Jonathan R. Dry, Jeanne Kehren, Pierre Validire, Jordi Rodón, Philippe Vielh, Michel Ducreux, Susan Galbraith, M. Lehnert, Amir Onn, Raanan Berger, Marco A. Pierotti, Angel Porgador, C.S. Pramesh, Dingwei Ye, André Lopes Carvalho, Gerald Batist, Thierry Le Chevalier, Philippe Morice, Benjamin Besse, Gilles Vassal, Andrew Mortlock, Johan Hansson, Ioana Berindan‐Neagoe, Robert Dann, Joel Haspel, Alexandru Irimie, Steve Laderman, Hovav Nechushtan, Amal Al‐Omari, Trent Haywood, Catherine Bresson, Khee Chee Soo, Iman Osman, Hilario Mata, J. Jack Lee, Komal Jhaveri, Guillaume Meurice, Gary A. Palmer, Ludovic Lacroix, Serge Koscielny, Karina Eterovic, Jean‐Yves Blay, Richard E. Buller, Alexander Eggermont, Richard L. Schilsky, John Mendelsohn, Jean‐Charles Soria, Mace L. Rothenberg, Jean‐Yves Scoazec, Waun Ki Hong, Razelle Kurzrock

Abstract

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.

Citations Over TimeTop 23% of 2015 papers

Abstract

Related Papers