2012
Effect of KRAS Oncogene Substitutions on Protein Behavior: Implications for Signaling and Clinical Outcome
Ihle NT, Byers LA, Kim ES, Saintigny P, Lee JJ, Blumenschein GR, Tsao A, Liu S, Larsen JE, Wang J, Diao L, Coombes KR, Chen L, Zhang S, Abdelmelek MF, Tang X, Papadimitrakopoulou V, Minna JD, Lippman SM, Hong WK, Herbst RS, Wistuba II, Heymach JV, Powis G. Effect of KRAS Oncogene Substitutions on Protein Behavior: Implications for Signaling and Clinical Outcome. Journal Of The National Cancer Institute 2012, 104: 228-239. PMID: 22247021, PMCID: PMC3274509, DOI: 10.1093/jnci/djr523.Peer-Reviewed Original ResearchMeSH KeywordsAspartic AcidCarcinoma, Non-Small-Cell LungCell Line, TumorClinical Trials, Phase II as TopicCysteineDisease-Free SurvivalGene Expression ProfilingGene Expression Regulation, NeoplasticGenes, rasGenetic VectorsGlycineHumansImmunoblottingImmunoprecipitationKaplan-Meier EstimateLentivirusLung NeoplasmsMicroarray AnalysisMolecular Targeted TherapyMutationProto-Oncogene Proteins c-aktRandomized Controlled Trials as TopicSignal TransductionTOR Serine-Threonine KinasesTreatment OutcomeValineConceptsNon-small cell lung cancerKirsten rat sarcoma viral oncogene homologProgression-free survivalNSCLC cell linesWild-type KrasMutant KrasRefractory non-small cell lung cancerWorse progression-free survivalRat sarcoma viral oncogene homologRas2 Kirsten rat sarcoma viral oncogene homologSarcoma viral oncogene homologKaplan-Meier curvesCell lung cancerReverse-phase protein array studiesKRas proteinsHuman bronchial epithelial cellsCancer cell growthPatient tumor samplesCell linesImmortalized human bronchial epithelial cellsBronchial epithelial cellsProtein array studiesTumor gene expressionEvaluable patientsClinical outcomes
2010
Combination Treatment with MEK and AKT Inhibitors Is More Effective than Each Drug Alone in Human Non-Small Cell Lung Cancer In Vitro and In Vivo
Meng J, Dai B, Fang B, Bekele BN, Bornmann WG, Sun D, Peng Z, Herbst RS, Papadimitrakopoulou V, Minna JD, Peyton M, Roth JA. Combination Treatment with MEK and AKT Inhibitors Is More Effective than Each Drug Alone in Human Non-Small Cell Lung Cancer In Vitro and In Vivo. PLOS ONE 2010, 5: e14124. PMID: 21124782, PMCID: PMC2993951, DOI: 10.1371/journal.pone.0014124.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic Combined Chemotherapy ProtocolsApoptosisBenzimidazolesCarcinoma, Non-Small-Cell LungCell CycleCell Line, TumorCell SurvivalDose-Response Relationship, DrugDrug SynergismFemaleHeterocyclic Compounds, 3-RingHumansLung NeoplasmsMiceMice, Inbred BALB CMice, NudeMitogen-Activated Protein Kinase KinasesProto-Oncogene Proteins c-aktSignal TransductionSurvival AnalysisTumor BurdenXenograft Model Antitumor AssaysConceptsNon-small cell lung cancerCell lung cancerCombination of AZD6244Lung cancer cell linesCombination therapyLung cancerCancer cell linesTumor growthTumor tissueHuman non-small cell lung cancerLung cancer cell growthCell linesHuman lung cancer cell linesSingle drug treatmentSynergistic antitumor activityHuman lung tumorsAnimal survival timeMean animal survival timeCancer cell growthXenograft tumor growthP-AKT expressionLung tumorsDrug treatmentDrug combinationsSurvival time
2003
Gefitinib: current and future status in cancer therapy.
Herbst RS, Kies MS. Gefitinib: current and future status in cancer therapy. Clinical Advances In Hematology And Oncology 2003, 1: 466-72. PMID: 16258434.Peer-Reviewed Original ResearchConceptsEpidermal growth factor receptorTumor growthEGFR tyrosine kinase inhibitorsCurrent clinical development statusOngoing clinical trialsCombination of gefitinibClinical development statusCancer cell growthHost-dependent processesGrowth factor receptorHormonal therapyStandard chemotherapyBiologic agentsDisease recurrenceCell lungSolid malignanciesClinical trialsTumor cell functionsViable drug targetNovel agentsPreclinical studiesClinical developmentTumor typesGefitinibKinase inhibitors
2002
ZD1839: targeting the epidermal growth factor receptor in cancer therapy
Herbst RS. ZD1839: targeting the epidermal growth factor receptor in cancer therapy. Expert Opinion On Investigational Drugs 2002, 11: 837-849. PMID: 12036427, DOI: 10.1517/13543784.11.6.837.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerEpidermal growth factor receptorCell lung cancerGrowth factor receptorFactor receptorLung cancerSmall-molecule epidermal growth factor receptor (EGFR) tyrosine kinase inhibitorTumor typesEpidermal growth factor receptor tyrosine kinase inhibitorsGrowth factor receptor tyrosine kinase inhibitorsAntitumour activityReceptor tyrosine kinase inhibitorsMeaningful antitumour activityAcceptable tolerability profilePaclitaxel/carboplatinPhase II studyThird-line treatmentFirst-line treatmentPhase III trialsGemcitabine/cisplatinClinical trial programPromising clinical activityCancer cell growthHost-dependent processesAdvanced disease