2019
Expression and clinical significance of PD-L1, B7-H3, B7-H4 and TILs in human small cell lung Cancer (SCLC)
Carvajal-Hausdorf D, Altan M, Velcheti V, Gettinger SN, Herbst RS, Rimm DL, Schalper KA. Expression and clinical significance of PD-L1, B7-H3, B7-H4 and TILs in human small cell lung Cancer (SCLC). Journal For ImmunoTherapy Of Cancer 2019, 7: 65. PMID: 30850021, PMCID: PMC6408760, DOI: 10.1186/s40425-019-0540-1.Peer-Reviewed Original ResearchMeSH KeywordsAgedAged, 80 and overB7 AntigensB7-H1 AntigenBiomarkers, TumorFemaleFluorescent Antibody TechniqueHumansKaplan-Meier EstimateLung NeoplasmsLymphocytes, Tumor-InfiltratingMaleMiddle AgedNeoplasm GradingNeoplasm StagingPrognosisRetrospective StudiesSmall Cell Lung CarcinomaV-Set Domain-Containing T-Cell Activation Inhibitor 1ConceptsSmall cell lung cancerCell lung cancerB7-H4B7-H3Lung cancerPD-L1Non-small cell lung cancerBackgroundSmall cell lung cancerAnti-tumor immune responseHuman small cell lung cancerQuantitative immunofluorescenceB7 family ligandsLevels of TILsMultiplexed quantitative immunofluorescenceLevels of CD3Effector T cellsImmune checkpoint blockersPromising clinical activityTissue microarray formatLymphocyte subsetsCheckpoint blockersOverall survivalLung malignancyClinicopathological variablesMarker levels
2018
Safety and clinical activity of atezolizumab monotherapy in metastatic non-small-cell lung cancer: final results from a phase I study
Horn L, Gettinger SN, Gordon MS, Herbst RS, Gandhi L, Felip E, Sequist LV, Spigel DR, Antonia SJ, Balmanoukian A, Cassier PA, Liu B, Kowanetz M, O'Hear C, Fassò M, Grossman W, Sandler A, Soria JC. Safety and clinical activity of atezolizumab monotherapy in metastatic non-small-cell lung cancer: final results from a phase I study. European Journal Of Cancer 2018, 101: 201-209. PMID: 30077125, DOI: 10.1016/j.ejca.2018.06.031.Peer-Reviewed Original ResearchConceptsTreatment-related adverse eventsBaseline PD-L1 expressionObjective response ratePD-L1 expressionPD-L1Immune cellsGrade treatment-related adverse eventsSurvival rateCell lung cancer cohortLong-term clinical benefitTumor-infiltrating immune cellsTumor cellsPhase IPrevious systemic therapySingle-agent atezolizumabCell lung cancerExploratory subgroup analysisLung cancer cohortAtezolizumab monotherapyAdverse eventsDurable responsesMedian durationSystemic therapyAnticancer immunityPD-1
2017
The HGF/c-MET Pathway Is a Driver and Biomarker of VEGFR-inhibitor Resistance and Vascular Remodeling in Non–Small Cell Lung Cancer
Cascone T, Xu L, Lin HY, Liu W, Tran HT, Liu Y, Howells K, Haddad V, Hanrahan E, Nilsson MB, Cortez MA, Giri U, Kadara H, Saigal B, Park YY, Peng W, Lee JS, Ryan AJ, Jüergensmeier JM, Herbst RS, Wang J, Langley RR, Wistuba II, Lee JJ, Heymach JV. The HGF/c-MET Pathway Is a Driver and Biomarker of VEGFR-inhibitor Resistance and Vascular Remodeling in Non–Small Cell Lung Cancer. Clinical Cancer Research 2017, 23: 5489-5501. PMID: 28559461, PMCID: PMC5600821, DOI: 10.1158/1078-0432.ccr-16-3216.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarcinoma, Non-Small-Cell LungCell Line, TumorClinical Trials, Phase II as TopicClinical Trials, Phase III as TopicDisease Models, AnimalDrug Resistance, NeoplasmGene Expression ProfilingHepatocyte Growth FactorHumansHypoxiaKaplan-Meier EstimateLung NeoplasmsMaleMiceMolecular Targeted TherapyMulticenter Studies as TopicNeovascularization, PathologicPrognosisProtein Kinase InhibitorsProto-Oncogene Proteins c-metReceptors, Vascular Endothelial Growth FactorSignal TransductionXenograft Model Antitumor AssaysConceptsNon-small cell lung cancerHepatocyte growth factorC-MetHGF/c-Met pathwayHuman non-small cell lung cancerResistance of NSCLCAngiogenic factor levelsHGF plasma levelsCancer cellsTumor microvascular densityCell lung cancerEffect of therapyTortuous blood vesselsTumor vascular bedC-Met pathwayTyrosine kinase inhibitorsTumor-associated stromaClin Cancer ResHuman lung adenocarcinomaMurine xenograft modelVEGFR-TKIClinical outcomesLung cancerPlasma levelsMicrovascular densityWhole-exome sequencing and immune profiling of early-stage lung adenocarcinoma with fully annotated clinical follow-up
Kadara H, Choi M, Zhang J, Parra ER, Rodriguez-Canales J, Gaffney SG, Zhao Z, Behrens C, Fujimoto J, Chow C, Yoo Y, Kalhor N, Moran C, Rimm D, Swisher S, Gibbons DL, Heymach J, Kaftan E, Townsend JP, Lynch TJ, Schlessinger J, Lee J, Lifton RP, Wistuba II, Herbst RS. Whole-exome sequencing and immune profiling of early-stage lung adenocarcinoma with fully annotated clinical follow-up. Annals Of Oncology 2017, 28: 75-82. PMID: 27687306, PMCID: PMC5982809, DOI: 10.1093/annonc/mdw436.Peer-Reviewed Original ResearchConceptsRecurrence-free survivalPoor recurrence-free survivalWhole-exome sequencingEarly-stage lung adenocarcinomaMutant lung adenocarcinomaLung adenocarcinomaImmune markersClinical outcomesExact testNatural killer cell infiltrationProportional hazards regression modelsGranzyme B levelsImmune marker analysisImmune profiling analysisPD-L1 expressionImmune-based therapiesTumoral PD-L1Hazards regression modelsKRAS mutant tumorsNormal lung tissuesMajority of deathsFisher's exact testHigh mutation burdenAnalysis of immunophenotypeRelevant molecular markers
2015
Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial
Herbst RS, Baas P, Kim DW, Felip E, Pérez-Gracia JL, Han JY, Molina J, Kim JH, Arvis CD, Ahn MJ, Majem M, Fidler MJ, de Castro G, Garrido M, Lubiniecki GM, Shentu Y, Im E, Dolled-Filhart M, Garon EB. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. The Lancet 2015, 387: 1540-1550. PMID: 26712084, DOI: 10.1016/s0140-6736(15)01281-7.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, Monoclonal, HumanizedAntineoplastic AgentsB7-H1 AntigenCarcinoma, Non-Small-Cell LungDisease-Free SurvivalDocetaxelDrug Administration ScheduleFemaleGene Expression Regulation, NeoplasticHumansKaplan-Meier EstimateLung NeoplasmsMaleMiddle AgedMolecular Targeted TherapyPatient SelectionTaxoidsTreatment OutcomeConceptsCell lung cancerProgression-free survivalPD-L1 expressionOverall survivalLung cancerPD-L1Tumor cellsMedian progression-free survivalTreatment-related adverse eventsEfficacy of pembrolizumabMedian overall survivalProlongs overall survivalNew treatment optionsAcademic medical centerPrimary endpointAdverse eventsProgressive diseasePatient populationTotal populationTreatment optionsPembrolizumabGrade 3Medical CenterEffective treatmentInteractive voice response systemE2F8 as a Novel Therapeutic Target for Lung Cancer
Park SA, Platt J, Lee JW, López-Giráldez F, Herbst RS, Koo JS. E2F8 as a Novel Therapeutic Target for Lung Cancer. Journal Of The National Cancer Institute 2015, 107: djv151. PMID: 26089541, PMCID: PMC4651101, DOI: 10.1093/jnci/djv151.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsCCAAT-Enhancer-Binding ProteinsCell Line, TumorCell ProliferationCell SurvivalChromatin ImmunoprecipitationFluorescent Antibody TechniqueGene Expression Regulation, NeoplasticHumansImmunoblottingKaplan-Meier EstimateLung NeoplasmsMiceMolecular Targeted TherapyNeoplastic Stem CellsPromoter Regions, GeneticRepressor ProteinsTissue Array AnalysisUbiquitin-Protein LigasesUp-RegulationXenograft Model Antitumor AssaysConceptsTarget genesCell cycle regulationNovel therapeutic targetPromoter activity assaysCell proliferationCancer cellsExpression of UHRF1Transcription activatorAntisense morpholinoChromatin immunoprecipitationCycle regulationTherapeutic targetEmbryonic developmentE2F membersHuman lung cancer cellsMicroarray analysisInvasion analysisLung cancer cellsDirect bindingTumor growthE2F8Activity assaysPublic databasesColony formationUHRF1A Novel Small-Molecule Inhibitor Targeting CREB-CBP Complex Possesses Anti-Cancer Effects along with Cell Cycle Regulation, Autophagy Suppression and Endoplasmic Reticulum Stress
Lee JW, Park HS, Park SA, Ryu SH, Meng W, Jürgensmeier JM, Kurie JM, Hong WK, Boyer JL, Herbst RS, Koo JS. A Novel Small-Molecule Inhibitor Targeting CREB-CBP Complex Possesses Anti-Cancer Effects along with Cell Cycle Regulation, Autophagy Suppression and Endoplasmic Reticulum Stress. PLOS ONE 2015, 10: e0122628. PMID: 25897662, PMCID: PMC4405579, DOI: 10.1371/journal.pone.0122628.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdenocarcinoma of LungAnilidesAntineoplastic AgentsApoptosis Regulatory ProteinsAutophagyAutophagy-Related Protein 7Bcl-2-Like Protein 11Cell Cycle CheckpointsCell Line, TumorCyclic AMP Response Element-Binding ProteinDrug Screening Assays, AntitumorEndoplasmic Reticulum StressHumansInhibitory Concentration 50Kaplan-Meier EstimateLung NeoplasmsMembrane ProteinsMolecular Docking SimulationOrganophosphatesPeptide FragmentsProportional Hazards ModelsProtein BindingProto-Oncogene ProteinsSialoglycoproteinsUbiquitin-Activating EnzymesConceptsLung cancerHuman lung cancer cell linesEndoplasmic reticulum (ER) stress markersLung cancer cell linesNovel therapeutic strategiesPotential therapeutic targetAnti-cancer effectsNovel small molecule inhibitorPotential therapeutic agentCyclic AMP response element binding proteinAccumulation of p62Response element-binding proteinEndoplasmic reticulum stressCancer cell linesCancer deathCommon subtypeCell cycle arrestLung adenocarcinomaNew therapiesTherapeutic strategiesSmall molecule inhibitorsTherapeutic targetElement-binding proteinStress markersTherapeutic agentsObjective Measurement and Clinical Significance of TILs in Non–Small Cell Lung Cancer
Schalper KA, Brown J, Carvajal-Hausdorf D, McLaughlin J, Velcheti V, Syrigos KN, Herbst RS, Rimm DL. Objective Measurement and Clinical Significance of TILs in Non–Small Cell Lung Cancer. Journal Of The National Cancer Institute 2015, 107: dju435. PMID: 25650315, PMCID: PMC4565530, DOI: 10.1093/jnci/dju435.Peer-Reviewed Original ResearchMeSH KeywordsAntigens, CD20Carcinoma, Non-Small-Cell LungCD3 ComplexCD8 AntigensConfounding Factors, EpidemiologicFluorescent DyesHumansIndolesKaplan-Meier EstimateLung NeoplasmsLymphocytes, Tumor-InfiltratingMicroscopy, FluorescencePredictive Value of TestsRetrospective StudiesT-Lymphocytes, CytotoxicConceptsTumor-infiltrating lymphocytesLevels of CD3TIL subtypesMultivariable analysisTumor sizeLonger survivalAssociation of TILsLevel of TILsNon-small cell lung cancerNon-small cell lung cancer samplesLocal immune effectsClinico-pathologic characteristicsImmune checkpoint inhibitorsCell lung cancerCell lung cancer samplesLung cancer samplesDifferent tumor compartmentsObjective measurementsElevated CD3High CD20TIL markersTIL subpopulationsCheckpoint inhibitorsSmoking historyHistology type
2013
Clinical and Biomarker Outcomes of the Phase II Vandetanib Study from the BATTLE Trial
Tsao AS, Liu S, Lee JJ, Alden CM, Blumenschein GR, Herbst R, Davis SE, Kim E, Lippman S, Heymach J, Tran H, Tang X, Wistuba I, Hong WK. Clinical and Biomarker Outcomes of the Phase II Vandetanib Study from the BATTLE Trial. Journal Of Thoracic Oncology 2013, 8: 658-661. PMID: 23584298, PMCID: PMC5118909, DOI: 10.1097/jto.0b013e31828d08ae.Peer-Reviewed Original ResearchMeSH KeywordsAcute-Phase ProteinsAgedAntineoplastic AgentsBiomarkers, TumorCarcinoma, Non-Small-Cell LungDisease-Free SurvivalFemaleGene AmplificationGenes, erbB-1HumansInterleukin-9Kaplan-Meier EstimateLipocalin-2LipocalinsLung NeoplasmsMaleMiddle AgedMutationPiperidinesProportional Hazards ModelsProto-Oncogene ProteinsProto-Oncogene Proteins p21(ras)QuinazolinesRas ProteinsTNF-Related Apoptosis-Inducing LigandConceptsDisease control rateWorse OSShorter PFSControl rateMutation patientsDual epidermal growth factor receptorVascular endothelial growth factor receptor inhibitionLung Cancer Elimination (BATTLE) trialNeutrophil gelatinase-associated lipocalinCell lung cancer patientsGrowth factor receptor inhibitionPhase II trialGelatinase-associated lipocalinLung cancer patientsTumor core biopsiesSerum biomarker analysisEGFR mutation patientsEpidermal growth factor receptorEGFR gene amplificationApoptosis-inducing ligandGrowth factor receptorMedian PFSOS benefitEpidermal growth factor receptor tyrosine kinaseII trial
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
Phase II Selection Design Trial of Concurrent Chemotherapy and Cetuximab Versus Chemotherapy Followed by Cetuximab in Advanced-Stage Non–Small-Cell Lung Cancer: Southwest Oncology Group Study S0342
Herbst RS, Kelly K, Chansky K, Mack PC, Franklin WA, Hirsch FR, Atkins JN, Dakhil SR, Albain KS, Kim ES, Redman M, Crowley JJ, Gandara DR. Phase II Selection Design Trial of Concurrent Chemotherapy and Cetuximab Versus Chemotherapy Followed by Cetuximab in Advanced-Stage Non–Small-Cell Lung Cancer: Southwest Oncology Group Study S0342. Journal Of Clinical Oncology 2010, 28: 4747-4754. PMID: 20921467, PMCID: PMC3020704, DOI: 10.1200/jco.2009.27.9356.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorCarboplatinCarcinoma, Non-Small-Cell LungCetuximabDisease-Free SurvivalDrug Administration ScheduleErbB ReceptorsErlotinib HydrochlorideFemaleHumansKaplan-Meier EstimateLung NeoplasmsMaleMiddle AgedMutationNeoplasm StagingPaclitaxelPatient SelectionProto-Oncogene ProteinsProto-Oncogene Proteins p21(ras)QuinazolinesRas ProteinsResearch DesignSouthwestern United StatesTreatment OutcomeConceptsCell lung cancerConcurrent chemotherapyLung cancerEpidermal growth factor receptor tyrosine kinase inhibitorsGrowth factor receptor tyrosine kinase inhibitorsProgression-free survival timeRandomized phase II trialReceptor tyrosine kinase inhibitorsMedian overall survivalPaclitaxel/carboplatinTreatment-naive patientsGrade 3 rashPhase II trialAdvanced-stage NSCLCPhase III evaluationTyrosine kinase inhibitorsEnhanced antitumor activityConcurrent regimenMaintenance cetuximabMedian followVersus ChemotherapyChemotherapy regimenII trialSequential therapyConcurrent therapyChemoradiotherapy With or Without AE-941 in Stage III Non–Small Cell Lung Cancer: A Randomized Phase III Trial
Lu C, Lee JJ, Komaki R, Herbst RS, Feng L, Evans WK, Choy H, Desjardins P, Esparaz BT, Truong MT, Saxman S, Kelaghan J, Bleyer A, Fisch MJ. Chemoradiotherapy With or Without AE-941 in Stage III Non–Small Cell Lung Cancer: A Randomized Phase III Trial. Journal Of The National Cancer Institute 2010, 102: 859-865. PMID: 20505152, PMCID: PMC2902826, DOI: 10.1093/jnci/djq179.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAngiogenesis InhibitorsAntineoplastic Combined Chemotherapy ProtocolsBiological ProductsCarcinoma, Non-Small-Cell LungCartilageChemotherapy, AdjuvantDisease-Free SurvivalDouble-Blind MethodFemaleHumansKaplan-Meier EstimateLung NeoplasmsMaleMiddle AgedMultivariate AnalysisNeoplasm StagingRadiotherapy, AdjuvantTissue ExtractsTreatment OutcomeConceptsNon-small cell lung cancerStage III non-small cell lung cancerUnresectable stage III non-small cell lung cancerProgression-free survivalTumor response rateCell lung cancerOverall survivalAE-941Lung cancerPlacebo groupClinical trialsUnresectable stage III NSCLC patientsResponse rateStage III NSCLC patientsPhase III clinical trialsAcademic oncology centerCommon grade 3Kaplan-Meier methodPhase III trialsShark cartilage extractTarget sample sizeToxic effectsChest radiotherapyConcurrent chemotherapyEligible patients
2009
Baseline Vascular Endothelial Growth Factor Concentration as a Potential Predictive Marker of Benefit from Vandetanib in Non–Small Cell Lung Cancer
Hanrahan EO, Ryan AJ, Mann H, Kennedy SJ, Langmuir P, Natale RB, Herbst RS, Johnson BE, Heymach JV. Baseline Vascular Endothelial Growth Factor Concentration as a Potential Predictive Marker of Benefit from Vandetanib in Non–Small Cell Lung Cancer. Clinical Cancer Research 2009, 15: 3600-3609. PMID: 19447868, DOI: 10.1158/1078-0432.ccr-08-2568.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorCarcinoma, Non-Small-Cell LungClinical Trials, Phase II as TopicEnzyme-Linked Immunosorbent AssayHumansKaplan-Meier EstimateLung NeoplasmsMeta-Analysis as TopicPiperidinesPredictive Value of TestsQuinazolinesRandomized Controlled Trials as TopicReceptors, Vascular Endothelial Growth FactorTreatment OutcomeVascular Endothelial Growth Factor AConceptsNon-small cell lung cancerProgression-free survivalCell lung cancerAdvanced non-small cell lung cancerVandetanib monotherapyLung cancerDisease progressionVEGF levelsVEGF valuesSimilar riskRandomized phase II studyVascular endothelial growth factor concentrationsExploratory retrospective analysisPhase II studyBaseline VEGF levelsPotential predictive markerLower VEGF levelsGrowth factor concentrationsBaseline VEGFCarboplatin-paclitaxelPFS advantageII studyPredictive markerRetrospective analysisHealthy subjects