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

Onderzoeksoutput: Bijdrage aan tijdschrift › Artikel › peer review

22 Citaten (Scopus)

Samenvatting

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.

Originele taal-2	Engels
Pagina's (van-tot)	14139-14152
Aantal pagina's	14
Tijdschrift	Oncotarget
Volume	6
Nummer van het tijdschrift	16
DOI's	https://doi.org/10.18632/oncotarget.3741
Status	Gepubliceerd - 2015
Extern gepubliceerd	Ja

Toegang tot document

10.18632/oncotarget.3741

Citeer dit

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

@article{9715f76630924e70b3cbd964a30af10b,

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.",

keywords = "Algorithm, NSCLC, Pathway, Targeted therapies, Tri-therapy",

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

year = "2015",

doi = "10.18632/oncotarget.3741",

language = "English",

volume = "6",

pages = "14139--14152",

journal = "Oncotarget",

issn = "1949-2553",

publisher = "Impact Journals LLC",

number = "16",

}

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, nr. 16, blz. 14139-14152. https://doi.org/10.18632/oncotarget.3741

TY - JOUR

T1 - A simplified interventional mapping system (SIMS) for the selection of combinations of targeted treatments in non-small cell lung cancer

AU - Lazar, Vladimir

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

PY - 2015

Y1 - 2015

N2 - 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.

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.

KW - Algorithm

KW - NSCLC

KW - Pathway

KW - Targeted therapies

KW - Tri-therapy

UR - http://www.scopus.com/inward/record.url?scp=84931037125&partnerID=8YFLogxK

U2 - 10.18632/oncotarget.3741

DO - 10.18632/oncotarget.3741

M3 - Article

C2 - 25944621

AN - SCOPUS:84931037125

SN - 1949-2553

VL - 6

SP - 14139

EP - 14152

JO - Oncotarget

JF - Oncotarget

IS - 16

ER -

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

Samenvatting

Toegang tot document

Vingerafdruk

Citeer dit