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An Epithelial–Mesenchymal Transition Gene Signature Predicts Resistance to EGFR and PI3K Inhibitors and Identifies Axl as a Therapeutic Target for Overcoming EGFR Inhibitor Resistance

Clinical Cancer Research · 2012 · Vol. 19(1) · pp. 279–290

Lauren A. Byers✉(The University of Texas MD Anderson Cancer Center)Lixia Diao(Astex Pharmaceuticals)Jing Wang(Northwestern University)Pierre Saintigny(Harold C. Simmons Comprehensive Cancer Center)Luc Girard(Astex Pharmaceuticals)Michael Peyton(Northwestern University)Li Shen(The University of Texas MD Anderson Cancer Center)You-Hong Fan(Northwestern University)Uma Giri(Tolero Pharmaceuticals (United States))Praveen K. Tumula(Harold C. Simmons Comprehensive Cancer Center)Monique B. Nilsson(Harold C. Simmons Comprehensive Cancer Center)Jayanthi Gudikote(The University of Texas MD Anderson Cancer Center)Hai T. Tran(Northwestern University)Robert J. Cardnell(Northwestern University)David J. Bearss(Harold C. Simmons Comprehensive Cancer Center)Steven L. Warner(Tolero Pharmaceuticals (United States))Jason M. Foulks(Astex Pharmaceuticals)Steven B. Kanner(Harold C. Simmons Comprehensive Cancer Center)Varsha Gandhi(Harold C. Simmons Comprehensive Cancer Center)Nancy Krett(Astex Pharmaceuticals)Steven T. Rosen(The University of Texas MD Anderson Cancer Center)Edward S. Kim(Tolero Pharmaceuticals (United States))Roy S. Herbst(Astex Pharmaceuticals)George R. Blumenschein(Harold C. Simmons Comprehensive Cancer Center)J. Jack Lee(The University of Texas MD Anderson Cancer Center)Scott M. Lippman(Astex Pharmaceuticals)K. Kian Ang(Harold C. Simmons Comprehensive Cancer Center)Gordon B. Mills(Astex Pharmaceuticals)Waun Ki Hong(Northwestern University)John N. Weinstein(Astex Pharmaceuticals)Ignacio I. Wistuba(The University of Texas MD Anderson Cancer Center)Kevin R. Coombes(Northwestern University)John D. Minna(Northwestern University)John V. Heymach✉(The University of Texas MD Anderson Cancer Center)

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Abstract

We have developed a robust EMT signature that predicts resistance to EGFR and PI3K/Akt inhibitors, highlights different patterns of drug responsiveness for epithelial and mesenchymal cells, and identifies Axl as a potential therapeutic target for overcoming EGFR inhibitor resistance associated with the mesenchymal phenotype.

Pancreatic and Hepatic Oncology Research Lung Cancer Treatments and Mutations Phagocytosis and Immune RegulationErlotinibEpithelial–mesenchymal transitionEGFR inhibitorsCancer researchMesenchymal stem cellGene signatureLung cancerPI3K/AKT/mTOR pathwayEpidermal growth factor receptorMedicine

MeSH terms

Phosphoinositide-3 Kinase InhibitorsAxl Receptor Tyrosine KinaseAnimalsCarcinoma, Non-Small-Cell LungHumansLung NeoplasmsNeoplasm MetastasisProto-Oncogene ProteinsRecurrenceReproducibility of ResultsCluster AnalysisDrug Resistance, NeoplasmProteomeReceptor Protein-Tyrosine KinasesGene Expression Profiling

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