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 Porgador; C. 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

doi:10.18632/oncotarget.3741

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 journal › Article › peer-review

22 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 language	English (US)
Pages (from-to)	14139-14152
Number of pages	14
Journal	Oncotarget
Volume	6
Issue number	16
DOIs	https://doi.org/10.18632/oncotarget.3741
State	Published - 2015

Keywords

Algorithm
NSCLC
Pathway
Targeted therapies
Tri-therapy

ASJC Scopus subject areas

Oncology

MD Anderson CCSG core facilities

Biostatistics Resource Group

Access to Document

10.18632/oncotarget.3741

Cite this

Lazar, V., Rubin, E., Depil, S., Pawitan, Y., Martini, J. F., Gomez-Navarro, J., Yver, A., Kan, Z., Dry, J. R., Kehren, J., Validire, P., Rodon, J., Vielh, P., Ducreux, M., Galbraith, S., Lehnert, M., Onn, A., Berger, R., Pierotti, M. A., ... Kurzrock, R. (2015). A simplified interventional mapping system (SIMS) for the selection of combinations of targeted treatments in non-small cell lung cancer. Oncotarget, 6(16), 14139-14152. https://doi.org/10.18632/oncotarget.3741

Lazar, V, Rubin, E, Depil, S, Pawitan, Y, Martini, JF, Gomez-Navarro, J, Yver, A, Kan, Z, Dry, JR, Kehren, J, Validire, P, Rodon, J, Vielh, P, Ducreux, M, Galbraith, S, Lehnert, M, Onn, A, Berger, R, Pierotti, MA, Porgador, A, Pramesh, CS, Ye, DW, Carvalho, AL, Batist, G, Chevalier, TL, Morice, P, Besse, B, Vassal, G, Mortlock, A, Hansson, J, Berindan-Neagoe, I, Dann, R, Haspel, J, Irimie, A, Laderman, S, Nechushtan, H, Al Omari, AS, Haywood, T, Bresson, C, Soo, KC, Osman, I, Mata, H, Lee, JJ, Jhaveri, K, Meurice, G, Palmer, G, Lacroix, L, Koscielny, S, Eterovic, KA, Blay, JY, Buller, R, Eggermont, A, Schilsky, RL, Mendelsohn, J, Soria, JC, Rothenberg, M, Scoazec, JY, Hong, WK & Kurzrock, R 2015, 'A simplified interventional mapping system (SIMS) for the selection of combinations of targeted treatments in non-small cell lung cancer', Oncotarget, vol. 6, no. 16, pp. 14139-14152. https://doi.org/10.18632/oncotarget.3741

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

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.",

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AU - Rubin, Eitan

AU - Depil, Stephane

AU - Pawitan, Yudi

AU - Martini, Jean François

AU - Gomez-Navarro, Jesus

AU - Yver, Antoine

AU - Kan, Zhengyin

AU - Dry, Jonathan R.

AU - Kehren, Jeanne

AU - Validire, Pierre

AU - Rodon, Jordi

AU - Vielh, Philippe

AU - Ducreux, Michel

AU - Galbraith, Susan

AU - Lehnert, Manfred

AU - Onn, Amir

AU - Berger, Raanan

AU - Pierotti, Marco A.

AU - Porgador, Angel

AU - Pramesh, C. S.

AU - Ye, Ding wei

AU - Carvalho, Andre L.

AU - Batist, Gerald

AU - Chevalier, Thierry Le

AU - Morice, Philippe

AU - Besse, Benjamin

AU - Vassal, Gilles

AU - Mortlock, Andrew

AU - Hansson, Johan

AU - Berindan-Neagoe, Ioana

AU - Dann, Robert

AU - Haspel, Joel

AU - Irimie, Alexandru

AU - Laderman, Steve

AU - Nechushtan, Hovav

AU - Al Omari, Amal S.

AU - Haywood, Trent

AU - Bresson, Catherine

AU - Soo, Khee Chee

AU - Osman, Iman

AU - Mata, Hilario

AU - Lee, Jack J.

AU - Jhaveri, Komal

AU - Meurice, Guillaume

AU - Palmer, Gary

AU - Lacroix, Ludovic

AU - Koscielny, Serge

AU - Eterovic, Karina Agda

AU - Blay, Jean Yves

AU - Buller, Richard

AU - Eggermont, Alexander

AU - Schilsky, Richard L.

AU - Mendelsohn, John

AU - Soria, Jean Charles

AU - Rothenberg, Mace

AU - Scoazec, Jean Yves

AU - Hong, Waun Ki

AU - Kurzrock, Razelle

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AB - 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.

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KW - NSCLC

KW - Pathway

KW - Targeted therapies

KW - Tri-therapy

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

Abstract

Keywords

ASJC Scopus subject areas

MD Anderson CCSG core facilities

Access to Document

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