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
2015
Co-occurring Genomic Alterations Define Major Subsets of KRAS-Mutant Lung Adenocarcinoma with Distinct Biology, Immune Profiles, and Therapeutic Vulnerabilities
Skoulidis F, Byers LA, Diao L, Papadimitrakopoulou VA, Tong P, Izzo J, Behrens C, Kadara H, Parra ER, Canales JR, Zhang J, Giri U, Gudikote J, Cortez MA, Yang C, Fan Y, Peyton M, Girard L, Coombes KR, Toniatti C, Heffernan TP, Choi M, Frampton GM, Miller V, Weinstein JN, Herbst RS, Wong KK, Zhang J, Sharma P, Mills GB, Hong WK, Minna JD, Allison JP, Futreal A, Wang J, Wistuba II, Heymach JV. Co-occurring Genomic Alterations Define Major Subsets of KRAS-Mutant Lung Adenocarcinoma with Distinct Biology, Immune Profiles, and Therapeutic Vulnerabilities. Cancer Discovery 2015, 5: 860-877. PMID: 26069186, PMCID: PMC4527963, DOI: 10.1158/2159-8290.cd-14-1236.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdenocarcinoma of LungAMP-Activated Protein Kinase KinasesAMP-Activated Protein KinasesCell Line, TumorCluster AnalysisDNA-Binding ProteinsGene ExpressionGene Expression ProfilingGenetic VariationGenomicsHumansInflammationLung NeoplasmsMutationOxidative StressPrognosisProtein Serine-Threonine KinasesRas ProteinsSignal TransductionTranscription FactorsTumor Suppressor ProteinsConceptsKRAS-mutant lung adenocarcinomaCo-occurring genomic alterationsLung adenocarcinomaDistinct biologyTherapeutic vulnerabilitiesSTK11/LKB1Hsp90 inhibitor therapyRelapse-free survivalDrug sensitivity patternsGenomic alterationsCDKN2A/BKC tumorsInflammatory markersMucinous histologyImmune markersImmune profilePD-L1AdenocarcinomaSensitivity patternMajor subsetNKX2-1 transcription factorLow expressionTumorsGenetic alterationsEffector molecules