Faculty Collaboration Database

A simplified interventional mapping system (SIMS) for the selection of combinations of targeted treatments in non-small cell lung cancer. Oncotarget 2015 Jun 10;6(16):14139-52

Date

05/07/2015

Pubmed ID

25944621

Pubmed Central ID

PMC4546456

DOI

10.18632/oncotarget.3741

Scopus ID

2-s2.0-84931037125 (requires institutional sign-in at Scopus site)   22 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.

Author List

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, Le Chevalier T, 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

Author

Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols
Carcinoma, Non-Small-Cell Lung
Female
Humans
Lung Neoplasms
Male
Middle Aged
Molecular Targeted Therapy
Precision Medicine
Transcriptome