2024
Transformation to small cell lung cancer is irrespective of EGFR and accelerated by SMAD4-mediated ASCL1 transcription independently of RB1 in non-small cell lung cancer
Ding X, Shi M, Liu D, Cao J, Zhang K, Zhang R, Zhang L, Ai K, Su B, Zhang J. Transformation to small cell lung cancer is irrespective of EGFR and accelerated by SMAD4-mediated ASCL1 transcription independently of RB1 in non-small cell lung cancer. Cell Communication And Signaling 2024, 22: 45. PMID: 38233864, PMCID: PMC10795321, DOI: 10.1186/s12964-023-01260-8.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerSmall cell lung cancerSmall cell lung cancer transformationCell lung cancerTransformation to small cell lung cancerLung cancerEGFR-mutant non-small cell lung cancerMYC inhibitorsNon-small cell lung cancer patientsMechanisms of TKI resistanceEGFR mutation statusResistant lung cancerNon-small cell lung cancer cellsDriver gene statusPhenotype in vitroCancer-related genesPotential functional genesPutative gene functionsCRISPR-Cas 9SCLC transformationTKI resistanceMutation statusNeuroendocrine phenotypeRB1 statusClinical characteristics
2021
Molecular Risk Stratification is Independent of EGFR Mutation Status in Identifying Early-Stage Non–Squamous Non–Small Cell Lung Cancer Patients at Risk for Recurrence and Likely to Benefit From Adjuvant Chemotherapy
Woodard GA, Kratz JR, Haro G, Gubens MA, Blakely CM, Jones KD, Mann MJ, Jablons DM. Molecular Risk Stratification is Independent of EGFR Mutation Status in Identifying Early-Stage Non–Squamous Non–Small Cell Lung Cancer Patients at Risk for Recurrence and Likely to Benefit From Adjuvant Chemotherapy. Clinical Lung Cancer 2021, 22: 587-595. PMID: 34544620, DOI: 10.1016/j.cllc.2021.08.008.Peer-Reviewed Original ResearchConceptsMolecular risk stratificationAdjuvant chemotherapyDisease-free survivalEGFR mutation statusAdjuvant interventionRisk stratificationEGFR patientsNSCLC patientsEGFR statusMutation statusSmall cell lung cancer patientsNon-squamous NSCLC patientsCell lung cancer patientsStage IA NSCLCStage IB patientsThird-generation TKIsEarly-stage NSCLCNon-Squamous NonLung cancer patientsEarly-stage cohortIB patientsProspective studyResidual diseaseCancer patientsEGFR mutationsMO01.13 Molecular Risk Stratification is Independent of EGFR Mutation Status in Identifying Early Stage Non-Squamous Non-Small Cell Lung Cancer Patients at Risk for Recurrence and Likely to Benefit from Adjuvant Chemotherapy
Woodard G, Kratz J, Haro G, Gubens M, Blakely C, Jones K, Mann M, Jablons D. MO01.13 Molecular Risk Stratification is Independent of EGFR Mutation Status in Identifying Early Stage Non-Squamous Non-Small Cell Lung Cancer Patients at Risk for Recurrence and Likely to Benefit from Adjuvant Chemotherapy. Journal Of Thoracic Oncology 2021, 16: s21. DOI: 10.1016/j.jtho.2020.10.061.Peer-Reviewed Original Research
2018
ADAURA: Phase III, Double-blind, Randomized Study of Osimertinib Versus Placebo in EGFR Mutation-positive Early-stage NSCLC After Complete Surgical Resection
Wu YL, Herbst R, Mann H, Rukazenkov Y, Marotti M, Tsuboi M. ADAURA: Phase III, Double-blind, Randomized Study of Osimertinib Versus Placebo in EGFR Mutation-positive Early-stage NSCLC After Complete Surgical Resection. Clinical Lung Cancer 2018, 19: e533-e536. PMID: 29789220, DOI: 10.1016/j.cllc.2018.04.004.Peer-Reviewed Original ResearchConceptsCell lung cancerDisease recurrenceLung cancerMutation statusSurvival rateEpidermal growth factor receptor tyrosine kinase inhibitorsGrowth factor receptor tyrosine kinase inhibitorsComplete surgical tumor resectionDisease-free survival ratesT790M mutation statusReceptor tyrosine kinase inhibitorsMaximum treatment durationStage IB-IIIAPlacebo-controlled studyDisease-free survivalEarly-stage NSCLCComplete surgical resectionOverall survival rateHealth-related qualityHealth resource useSurgical tumor resectionEGFR mutation statusTyrosine kinase inhibitorsCentral confirmationVersus Placebo
2017
Factors associated with better overall survival (OS) in patients with previously treated, PD-L1–expressing, advanced NSCLC: Multivariate analysis of KEYNOTE-010.
Herbst R, Baas P, Kim D, Felip E, Perez-Gracia J, Han J, Molina J, Kim J, Dubos Arvis C, Ahn M, Majem M, Fidler M, Castro G, Garrido M, Ellison M, Samkari A, Lubiniecki G, Garon E. Factors associated with better overall survival (OS) in patients with previously treated, PD-L1–expressing, advanced NSCLC: Multivariate analysis of KEYNOTE-010. Journal Of Clinical Oncology 2017, 35: 9090-9090. DOI: 10.1200/jco.2017.35.15_suppl.9090.Peer-Reviewed Original ResearchOverall survivalKEYNOTE-010Advanced NSCLCPD-L1Multivariate analysisPembrolizumab armBetter OSHazard ratioCox proportional hazards regression modelNormal baseline lactate dehydrogenaseProportional hazards regression modelsBaseline lactate dehydrogenasePD-L1 TPSPositive advanced NSCLCSuperior overall survivalBetter overall survivalIndependent central reviewHazards regression modelsLactate dehydrogenaseEGFR mutation statusNonsquamous histologyRECIST v1.1Smoking statusTumor characteristicsCentral review
2013
Quantitative Analysis of [11C]-Erlotinib PET Demonstrates Specific Binding for Activating Mutations of the EGFR Kinase Domain
Petrulli JR, Sullivan JM, Zheng MQ, Bennett DC, Charest J, Huang Y, Morris ED, Contessa JN. Quantitative Analysis of [11C]-Erlotinib PET Demonstrates Specific Binding for Activating Mutations of the EGFR Kinase Domain. Neoplasia 2013, 15: 1347-1353. PMID: 24403856, PMCID: PMC3884525, DOI: 10.1593/neo.131666.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarbon RadioisotopesCatalytic DomainCell Line, TumorDrug Evaluation, PreclinicalErbB ReceptorsErlotinib HydrochlorideGene ExpressionHumansMiceMice, NudeMutation, MissenseNeoplasm TransplantationPhosphorylationPositron-Emission TomographyProtein BindingProtein Processing, Post-TranslationalQuinazolinesRadiopharmaceuticalsConceptsNon-small cell lung cancerEpidermal growth factor receptorPositron emission tomographyMutant non-small cell lung cancerNovel clinical methodologyCell lung cancerMutations of EGFREGFR mutation statusDomain mutationsHuman cancer xenograftsKinase domain mutationsConstitutive EGFR phosphorylationMultiple tumor typesPET scan analysisMolecular imaging approachesExtracellular domain mutationsWild-type epidermal growth factor receptorSimplified reference tissue modelGrowth factor receptorReference tissue modelNSCLC xenograftsLung cancerCancer xenograftsMalignant gliomasClinical utilityCirculating MicroRNAs in Relation to EGFR Status and Survival of Lung Adenocarcinoma in Female Non-Smokers
Zhang H, Su Y, Xu F, Kong J, Yu H, Qian B. Circulating MicroRNAs in Relation to EGFR Status and Survival of Lung Adenocarcinoma in Female Non-Smokers. PLOS ONE 2013, 8: e81408. PMID: 24282590, PMCID: PMC3839880, DOI: 10.1371/journal.pone.0081408.Peer-Reviewed Original ResearchConceptsLung adenocarcinomaOverall survivalFemale patientsMiR-195MiR-122Survival outcomesPlasma levelsEGFR statusNon-smoking female patientsCox proportional hazards regressionKaplan-Meier survival analysisEGFR-mutant patientsProportional hazards regressionAdvanced disease stageEGFR mutation statusTime-dependent receiverMiR-122 expressionReal-time RT-PCRHazards regressionPoor prognosisPrognostic valueDisease stageNon smokersMutant patientsEGFR mutationsAn 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
2009
A phase II trial of IPI-504 (retaspimycin hydrochloride), a novel Hsp90 inhibitor, in patients with relapsed and/or refractory stage IIIb or stage IV non-small cell lung cancer (NSCLC) stratified by EGFR mutation status
Sequist L, Gettinger S, Natale R, Martins R, Lilenbaum R, Jänne P, Gray J, Samuel T, Grayzel D, Lynch T. A phase II trial of IPI-504 (retaspimycin hydrochloride), a novel Hsp90 inhibitor, in patients with relapsed and/or refractory stage IIIb or stage IV non-small cell lung cancer (NSCLC) stratified by EGFR mutation status. Journal Of Clinical Oncology 2009, 27: 8073-8073. DOI: 10.1200/jco.2009.27.15_suppl.8073.Peer-Reviewed Original ResearchNon-small cell lung cancerPhase II trialIPI-504Anti-tumor activityStable diseaseStage IIIBII trialPartial responseStage IV non-small cell lung cancerAdvanced non-small cell lung cancerCommon related adverse eventsIndependent radiology reviewAntitumor activityRelated adverse eventsCell lung cancerEGFR mutation analysisEGFR mutation statusHeat shock protein 90 inhibitorNSCLC cell linesShock protein 90 inhibitorsMurine xenograft modelCohort expansionEligible patientsNovel Hsp90 inhibitorPrior therapy
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