2017
Stress hormones promote EGFR inhibitor resistance in NSCLC: Implications for combinations with β-blockers
Nilsson MB, Sun H, Diao L, Tong P, Liu D, Li L, Fan Y, Poteete A, Lim SO, Howells K, Haddad V, Gomez D, Tran H, Pena GA, Sequist LV, Yang JC, Wang J, Kim ES, Herbst R, Lee JJ, Hong WK, Wistuba I, Hung MC, Sood AK, Heymach JV. Stress hormones promote EGFR inhibitor resistance in NSCLC: Implications for combinations with β-blockers. Science Translational Medicine 2017, 9 PMID: 29118262, PMCID: PMC5870120, DOI: 10.1126/scitranslmed.aao4307.Peer-Reviewed Original ResearchMeSH KeywordsAdrenergic beta-AntagonistsAfatinibAMP-Activated Protein Kinase KinasesCarcinoma, Non-Small-Cell LungCell Line, TumorCyclic AMP Response Element-Binding ProteinDrug Resistance, NeoplasmEpinephrineErbB ReceptorsHumansInterleukin-6Lung NeoplasmsMutationNorepinephrineProtein Kinase CProtein Kinase InhibitorsProtein Serine-Threonine KinasesQuinazolinesReceptors, Adrenergic, betaSignal TransductionXenograft Model Antitumor AssaysConceptsNon-small cell lung cancerEGFR inhibitor resistanceΒ-blockersInhibitor resistanceStress hormonesLiver kinase B1Epidermal growth factor receptor tyrosine kinase inhibitor resistanceLower IL-6 concentrationsΒ-blocker useIL-6 concentrationsIL-6 inhibitionCell lung cancerTyrosine kinase inhibitor resistanceEGFR-TKI resistanceInterleukin-6 expressionKinase inhibitor resistanceChronic stress hormonesNSCLC patientsEGFR-TKIIL-6Lung cancerAR activationWorse outcomesNSCLC cellsTKI resistance
2013
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
Byers LA, Diao L, Wang J, Saintigny P, Girard L, Peyton M, Shen L, Fan Y, Giri U, Tumula PK, Nilsson MB, Gudikote J, Tran H, Cardnell RJ, Bearss DJ, Warner SL, Foulks JM, Kanner SB, Gandhi V, Krett N, Rosen ST, Kim ES, Herbst RS, Blumenschein GR, Lee JJ, Lippman SM, Ang KK, Mills GB, Hong WK, Weinstein JN, Wistuba II, Coombes KR, Minna JD, Heymach JV. 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 2013, 19: 279-290. PMID: 23091115, PMCID: PMC3567921, DOI: 10.1158/1078-0432.ccr-12-1558.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAxl Receptor Tyrosine KinaseCarcinoma, Non-Small-Cell LungCell Line, TumorCluster AnalysisDrug Resistance, NeoplasmEpithelial-Mesenchymal TransitionErbB ReceptorsGene Expression ProfilingHumansLung NeoplasmsMiceNeoplasm MetastasisPhosphoinositide-3 Kinase InhibitorsProtein Kinase InhibitorsProteomeProteomicsProto-Oncogene ProteinsReceptor Protein-Tyrosine KinasesRecurrenceReproducibility of ResultsConceptsEpithelial-mesenchymal transitionPotential therapeutic targetEGFR inhibitor resistanceTherapeutic targetEMT signatureInhibitor resistanceMesenchymal transition gene signatureMesenchymal cellsCell linesBiomarker-Integrated ApproachesPI3K/Akt pathway inhibitorNon-small cell lung carcinoma cell lineEGFR mutation statusReceptor tyrosine kinase AXLNSCLC cell linesPI3K/Akt inhibitorCell lung carcinoma cell lineGene expression profilesTyrosine kinase AXLLung carcinoma cell linePI3K inhibitorsDrug response analysisAkt pathway inhibitorCarcinoma cell linesErlotinib resistance