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

Vladimir Lazar, Eitan Rubin, Stephane Depil, Yudi Pawitan, Jean François Martini, Jesus Gomez-Navarro, Antoine Yver, Zhengyin Kan, Jonathan R. Dry, Jeanne Kehren, Pierre Validire, Jordi Rodon, Philippe Vielh, Michel Ducreux, Susan Galbraith, Manfred Lehnert, Amir Onn, Raanan Berger, Marco A. Pierotti, Angel PorgadorC. S. Pramesh, Ding wei Ye, Andre L. 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 S. Al Omari, Trent Haywood, Catherine Bresson, Khee Chee Soo, Iman Osman, Hilario Mata, Jack J. Lee, Komal Jhaveri, Guillaume Meurice, Gary Palmer, Ludovic Lacroix, Serge Koscielny, Karina Agda Eterovic, Jean Yves Blay, Richard Buller, Alexander Eggermont, Richard L. Schilsky, John Mendelsohn, Jean Charles Soria, Mace Rothenberg, Jean Yves Scoazec, Waun Ki Hong, Razelle Kurzrock

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

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.

Original languageEnglish
Pages (from-to)14139-14152
Number of pages14
JournalOncotarget
Volume6
Issue number16
DOIs
StatePublished - 1 Jan 2015

Keywords

  • Algorithm
  • NSCLC
  • Pathway
  • Targeted therapies
  • Tri-therapy

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