2022
Development of an immunohistochemical assay for Siglec-15
Shafi S, Aung TN, Robbins C, Zugazagoitia J, Vathiotis I, Gavrielatou N, Yaghoobi V, Fernandez A, Niu S, Liu LN, Cusumano ZT, Leelatian N, Cole K, Wang H, Homer R, Herbst RS, Langermann S, Rimm DL. Development of an immunohistochemical assay for Siglec-15. Laboratory Investigation 2022, 102: 771-778. PMID: 35459795, PMCID: PMC9253057, DOI: 10.1038/s41374-022-00785-9.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalB7-H1 AntigenCarcinoma, Non-Small-Cell LungHumansImmunohistochemistryLung NeoplasmsSialic Acid Binding Immunoglobulin-like LectinsConceptsSiglec-15IHC assaysPD-L1PD-1/PD-L1 inhibitionPD-L1 blockadePD-L1 inhibitionHigh expressionFuture clinical trialsImmunoglobulin-type lectinsSiglec-15 expressionCompanion diagnostic assayPromising new targetTumor histologyImmunotherapeutic targetLung cancerImmune cellsClinical trialsNovel recombinant antibodiesCancer histologyImmunohistochemical assaysMyeloid cellsTumor typesScoring systemNew targetsHigh concordance
2017
B7-H3 Expression in NSCLC and Its Association with B7-H4, PD-L1 and Tumor-Infiltrating Lymphocytes
Altan M, Pelekanou V, Schalper KA, Toki M, Gaule P, Syrigos K, Herbst RS, Rimm DL. B7-H3 Expression in NSCLC and Its Association with B7-H4, PD-L1 and Tumor-Infiltrating Lymphocytes. Clinical Cancer Research 2017, 23: 5202-5209. PMID: 28539467, PMCID: PMC5581684, DOI: 10.1158/1078-0432.ccr-16-3107.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedB7 AntigensB7-H1 AntigenBiomarkers, TumorCarcinoma, Non-Small-Cell LungCell Line, TumorDisease-Free SurvivalFemaleGene Expression Regulation, NeoplasticHumansImmunohistochemistryLymphocytes, Tumor-InfiltratingMaleMiddle AgedPrognosisV-Set Domain-Containing T-Cell Activation Inhibitor 1ConceptsNon-small cell lung cancerTumor-infiltrating lymphocytesB7-H3 proteinB7-H4PD-L1B7-H3Majority of NSCLCQuantitative immunofluorescenceImmune checkpoints PD-1Major clinicopathologic variablesLevels of CD3Negative prognostic impactCell lung cancerPoor overall survivalSuccessful therapeutic targetsB7 family membersClin Cancer ResB7-H1NSCLC cohortOverall survivalPrognostic impactSmoking historyClinicopathologic characteristicsPD-1Clinical stageWhole-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 markersMutation profiles in early-stage lung squamous cell carcinoma with clinical follow-up and correlation with markers of immune function
Choi M, Kadara H, Zhang J, Parra ER, Rodriguez-Canales J, Gaffney SG, Zhao Z, Behrens C, Fujimoto J, Chow C, Kim K, Kalhor N, Moran C, Rimm D, Swisher S, Gibbons DL, Heymach J, Kaftan E, Townsend JP, Lynch TJ, Schlessinger J, Lee J, Lifton RP, Herbst RS, Wistuba II. Mutation profiles in early-stage lung squamous cell carcinoma with clinical follow-up and correlation with markers of immune function. Annals Of Oncology 2017, 28: 83-89. PMID: 28177435, PMCID: PMC6246501, DOI: 10.1093/annonc/mdw437.Peer-Reviewed Original ResearchConceptsLung squamous cell carcinomaEarly stage lung squamous cell carcinomaNon-small cell lung cancerSquamous cell carcinomaWhole-exome sequencingImmune markersClinical outcomesCell carcinomaPIK3CA mutationsExact testPoor recurrence-free survivalProportional hazards regression modelsTumoral PD-L1 expressionPD-L1 expressionRecurrence-free survivalCell lung cancerComprehensive immune profilingTP53 mutant tumorsHazards regression modelsNormal lung tissuesFisher's exact testLUSC cohortAdjuvant therapyImmune profilingPoor prognosis
2016
Quantitative Assessment of the Heterogeneity of PD-L1 Expression in Non–Small-Cell Lung Cancer
McLaughlin J, Han G, Schalper KA, Carvajal-Hausdorf D, Pelakanou V, Rehman J, Velcheti V, Herbst R, LoRusso P, Rimm DL. Quantitative Assessment of the Heterogeneity of PD-L1 Expression in Non–Small-Cell Lung Cancer. JAMA Oncology 2016, 2: 1-9. PMID: 26562159, PMCID: PMC4941982, DOI: 10.1001/jamaoncol.2015.3638.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntibodies, MonoclonalAntibody SpecificityB7-H1 AntigenBiomarkers, TumorCarcinoma, Non-Small-Cell LungFemaleFluorescent Antibody TechniqueHumansImmunohistochemistryLung NeoplasmsMaleObserver VariationPredictive Value of TestsReproducibility of ResultsRetrospective StudiesTissue Array AnalysisConceptsTumor-infiltrating lymphocytesPD-L1 expressionPD-L1 antibodiesPD-L1 protein expressionCell lung cancerPD-L1Whole tissue sectionsQuantitative immunofluorescenceLung cancerChromogenic immunohistochemistryPoor concordanceDifferent PD-L1 antibodiesHigh tumor-infiltrating lymphocytesTumor PD-L1 expressionPD-L1 protein levelsCell lung cancer biopsiesMonoclonal antibodiesCurrent consensus guidelinesProtein expressionDurable clinical responsesMain outcome measuresEarly phase trialsLung cancer biopsiesRabbit monoclonal antibodyCorresponding tissue microarrays
2015
Role of Chitinase 3–like-1 and Semaphorin 7a in Pulmonary Melanoma Metastasis
Ma B, Herzog EL, Lee CG, Peng X, Lee CM, Chen X, Rockwell S, Koo JS, Kluger H, Herbst RS, Sznol M, Elias JA. Role of Chitinase 3–like-1 and Semaphorin 7a in Pulmonary Melanoma Metastasis. Cancer Research 2015, 75: 487-496. PMID: 25511377, PMCID: PMC4321965, DOI: 10.1158/0008-5472.can-13-3339.Peer-Reviewed Original ResearchConceptsMelanoma lung metastasisPulmonary melanoma metastasesPulmonary metastasesLung metastasesMelanoma metastasesGenetic deletionBreast cancer cellsPlexin C1 receptorsPulmonary microenvironmentPoor prognosisSemaphorin 7AMelanoma spreadChitinase 3MetastasisCHI3L1Cancer progressionSema7AInhibitory wayCancer cellsReceptorsSignificant reductionΒ1 integrinNovel pathwayCritical roleIL13Rα2
2013
Programmed death ligand-1 expression in non-small cell lung cancer
Velcheti V, Schalper KA, Carvajal DE, Anagnostou VK, Syrigos KN, Sznol M, Herbst RS, Gettinger SN, Chen L, Rimm DL. Programmed death ligand-1 expression in non-small cell lung cancer. Laboratory Investigation 2013, 94: 107-116. PMID: 24217091, PMCID: PMC6125250, DOI: 10.1038/labinvest.2013.130.Peer-Reviewed Original ResearchMeSH KeywordsAgedB7-H1 AntigenBiomarkers, TumorCarcinoma, Non-Small-Cell LungCell Line, TumorChi-Square DistributionCohort StudiesConnecticutFemaleGreeceHumansImmunohistochemistryLung NeoplasmsLymphocytes, Tumor-InfiltratingMalePrognosisReproducibility of ResultsRNA, MessengerSurvival AnalysisTissue Array AnalysisConceptsNon-small cell lung cancerPD-L1 expressionCell lung cancerPD-L1Tissue microarrayBetter outcomesNSCLC casesLung cancerDeath ligand 1 (PD-L1) expressionCell death ligand 1PD-L1 protein expressionEarly phase clinical trialsLigand 1 expressionTumor-infiltrating lymphocytesDeath ligand 1Significant better outcomePD-L1 mRNAPD-L1 proteinPhase clinical trialsNormal human placentaPrediction of responseQuantitative fluorescence approachesFrequency of expressionPD-1Prognostic value
2012
Targeting the Apoptotic Pathway in Chondrosarcoma Using Recombinant Human Apo2L/TRAIL (Dulanermin), a Dual Proapoptotic Receptor (DR4/DR5) Agonist
Subbiah V, Brown RE, Buryanek J, Trent J, Ashkenazi A, Herbst R, Kurzrock R. Targeting the Apoptotic Pathway in Chondrosarcoma Using Recombinant Human Apo2L/TRAIL (Dulanermin), a Dual Proapoptotic Receptor (DR4/DR5) Agonist. Molecular Cancer Therapeutics 2012, 11: 2541-2546. PMID: 22914439, PMCID: PMC3496030, DOI: 10.1158/1535-7163.mct-12-0358.Peer-Reviewed Original ResearchMeSH KeywordsApoptosisBone NeoplasmsCell SurvivalChondrosarcomaDNA Mutational AnalysisHumansImmunohistochemistryIsocitrate DehydrogenaseLung NeoplasmsMaleMiddle AgedProteomicsProto-Oncogene Proteins c-bcl-2Radiography, ThoracicReceptors, Death DomainRecombinant ProteinsSignal TransductionTNF-Related Apoptosis-Inducing LigandTomography, X-Ray ComputedTreatment OutcomeConceptsRecombinant human Apo2L/TRAILApo2L/TRAILRecent computed tomography scanSustained partial responseEvidence of diseaseComputed tomography scanP-ERK 1/2Partial responseProgressive diseaseNF-κBp65Receptor agonistTomography scanSubcentimeter nodulesPatient tumorsMetastatic chondrosarcomaP-mTORPatientsProlonged responseP-STAT3Proapoptotic receptor agonistsChondrosarcomaBcl-2DulanerminLungTumors
2011
Evaluation of pharmacodynamic biomarkers in a Phase 1a trial of dulanermin (rhApo2L/TRAIL) in patients with advanced tumours
Pan Y, Xu R, Peach M, Huang CP, Branstetter D, Novotny W, Herbst RS, Eckhardt SG, Holland PM. Evaluation of pharmacodynamic biomarkers in a Phase 1a trial of dulanermin (rhApo2L/TRAIL) in patients with advanced tumours. British Journal Of Cancer 2011, 105: 1830-1838. PMID: 22033270, PMCID: PMC3251880, DOI: 10.1038/bjc.2011.456.Peer-Reviewed Original ResearchConceptsCell death markersAdvanced tumorsPharmacodynamic biomarkersApoptotic markersPhase 1a studyPhase 1a trialDeath receptors DR4Colo205 tumorsSerum 8Patients 24Active caspase-3Patient seraColo205 xenograftsEvidence of activitySubsequent cell deathCytokeratin 18PatientsTransient increaseDulanerminReceptors DR4TumorsCaspase-3SerumCaspase-3/7Significant increase
2008
Epidermal growth factor receptor expression analysis in chemotherapy-naive patients with advanced non-small-cell lung cancer treated with gefitinib or placebo in combination with platinum-based chemotherapy
Giaccone G, Iacona RB, Fandi A, Janas M, Ochs JS, Herbst RS, Johnson DH. Epidermal growth factor receptor expression analysis in chemotherapy-naive patients with advanced non-small-cell lung cancer treated with gefitinib or placebo in combination with platinum-based chemotherapy. Journal Of Cancer Research And Clinical Oncology 2008, 135: 467-476. PMID: 18787840, DOI: 10.1007/s00432-008-0466-3.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsBiopsyCarcinoma, Non-Small-Cell LungCell DivisionErbB ReceptorsGefitinibGene Expression Regulation, NeoplasticHumansImmunohistochemistryLung NeoplasmsNeoplasm StagingPlacebosPlatinum CompoundsPrognosisQuinazolinesSurvival AnalysisConceptsPlatinum-based chemotherapyCell lung cancerPrognostic factorsLung cancerFirst-line platinum-based chemotherapyEpidermal growth factor receptor stainingChemotherapy-naive patientsPlacebo-controlled trialCox regression analysisReceptor expression analysisStrong prognostic indicatorMembrane stainingEGFR expression correlatesSurvival benefitImproved survivalPrognostic effectGrowth patternPredictive factorsPrognostic indicatorReceptor stainingPoor survivalTreatment groupsEGFR PharmDxEGFR expressionGefitinibMolecular Characteristics of Bronchioloalveolar Carcinoma and Adenocarcinoma, Bronchioloalveolar Carcinoma Subtype, Predict Response to Erlotinib
Miller VA, Riely GJ, Zakowski MF, Li AR, Patel JD, Heelan RT, Kris MG, Sandler AB, Carbone DP, Tsao A, Herbst RS, Heller G, Ladanyi M, Pao W, Johnson DH. Molecular Characteristics of Bronchioloalveolar Carcinoma and Adenocarcinoma, Bronchioloalveolar Carcinoma Subtype, Predict Response to Erlotinib. Journal Of Clinical Oncology 2008, 26: 1472-1478. PMID: 18349398, DOI: 10.1200/jco.2007.13.0062.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdenocarcinoma, Bronchiolo-AlveolarAdultAgedAged, 80 and overAntineoplastic AgentsBiomarkers, TumorDisease-Free SurvivalErbB ReceptorsErlotinib HydrochlorideFemaleHumansImmunohistochemistryLung NeoplasmsMaleMiddle AgedMutationProtein Kinase InhibitorsProto-Oncogene ProteinsProto-Oncogene Proteins p21(ras)QuinazolinesRas ProteinsSuppressor of Cytokine Signaling ProteinsTreatment OutcomeConceptsProgression-free survivalBronchioloalveolar carcinomaResponse rateEGFR mutationsEGFR immunohistochemistryKRAS mutationsEpidermal growth factor receptor (EGFR) mutationsPrimary end pointEfficacy of erlotinibPhase II trialSubset of patientsCell lung cancerBAC subtypeOverall response rateKRAS mutation statusPure bronchioloalveolar carcinomaBronchioloalveolar carcinoma (BAC) subtypeMolecular characteristicsMedian OSII trialMedian survivalOverall survivalHistologic subtypeLung cancerUnivariate analysis
2005
Tumor Cavitation in Stage I Non–Small Cell Lung Cancer: Epidermal Growth Factor Receptor Expression and Prediction of Poor Outcome
Onn A, Choe DH, Herbst RS, Correa AM, Munden RF, Truong MT, Vaporciyan AA, Isobe T, Gilcrease MZ, Marom EM. Tumor Cavitation in Stage I Non–Small Cell Lung Cancer: Epidermal Growth Factor Receptor Expression and Prediction of Poor Outcome. Radiology 2005, 237: 342-7. PMID: 16183941, DOI: 10.1148/radiol.2371041650.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaCarcinoma, Non-Small-Cell LungCarcinoma, Squamous CellErbB ReceptorsFemaleFollow-Up StudiesHumansImmunohistochemistryLung NeoplasmsMaleMiddle AgedNeoplasm StagingPrognosisProportional Hazards ModelsRadiography, ThoracicReceptor, ErbB-2Retrospective StudiesSurvival RateTomography, X-Ray ComputedConceptsStage I non-small cell lung cancerNon-small cell lung cancerEpidermal growth factor receptorCell lung cancerSquamous cell carcinomaCavitary lesionsTumor diameterCell carcinomaLung cancerSurvival timePathologic stage I non-small cell lung cancerEGFR overexpressionProportional hazards regression modelsShorter disease-free survival timeShorter overall survival timeDisease-free survival timeEpidermal growth factor receptor expressionFindings of chestGrowth factor receptor expressionMedian overall survivalOverall survival timeHazards regression modelsPresence of calcificationFactor receptor expressionInstitutional review board
2002
Non-small cell lung cancer clinical trials with trastuzumab: their foundation and preliminary results
Zinner RG, Kim J, Herbst RS. Non-small cell lung cancer clinical trials with trastuzumab: their foundation and preliminary results. Lung Cancer 2002, 37: 17-27. PMID: 12057863, DOI: 10.1016/s0169-5002(02)00035-1.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerHER2 overexpressionClinical trialsHER2-overexpressing metastatic breast cancerAntibody-dependent cell-mediated cytotoxicityMetastatic breast cancer trialsRandomized phase II trialRecombinant humanized monoclonal antibodyActivity of trastuzumabNSCLC clinical specimensPhase II studyPhase II trialEfficacy of trastuzumabMetastatic breast cancerBreast cancer trialsCell lung cancerCell-mediated cytotoxicityPoor clinical outcomeTreatment of patientsLung cancer clinical trialsHumanized monoclonal antibodyCombination of chemotherapyOverexpression of HER2Cancer clinical trialsDownregulation of HER2
2000
Treatment for malignant pleural effusion of human lung adenocarcinoma by inhibition of vascular endothelial growth factor receptor tyrosine kinase phosphorylation.
Yano S, Herbst RS, Shinohara H, Knighton B, Bucana CD, Killion JJ, Wood J, Fidler IJ. Treatment for malignant pleural effusion of human lung adenocarcinoma by inhibition of vascular endothelial growth factor receptor tyrosine kinase phosphorylation. Clinical Cancer Research 2000, 6: 957-65. PMID: 10741721.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAngiogenesis InhibitorsAnimalsCapillary PermeabilityCell DivisionCell LineEndothelial Growth FactorsEndothelium, VascularGene Expression RegulationHumansImmunohistochemistryIn Situ HybridizationLung NeoplasmsLymphokinesMaleMiceMice, Inbred BALB CMice, NudeNeoplasm TransplantationNeovascularization, PathologicPhosphorylationPhthalazinesPleural Effusion, MalignantPyridinesReceptor Protein-Tyrosine KinasesReceptors, Growth FactorReceptors, Vascular Endothelial Growth FactorTransplantation, HeterologousTumor Cells, CulturedVascular Endothelial Growth Factor AVascular Endothelial Growth FactorsConceptsMalignant pleural effusionReceptor tyrosine kinase inhibitorsPleural effusionPTK 787Human dermal microvascular endothelial cellsTyrosine kinase inhibitorsPC14PE6 cellsDermal microvascular endothelial cellsMicrovascular endothelial cellsVEGF/VPFOral treatmentLung lesionsGrowth factor receptor tyrosine kinase inhibitorsAdvanced human lung cancerPlatelet-derived growth factor receptor tyrosine kinase inhibitorVEGF/VPF proteinEndothelial cellsKinase inhibitorsVascular endothelial growth factor/vascular permeability factorHuman lung cancerNude mouse modelHuman lung adenocarcinomaHuman lung adenocarcinoma cellsVascular permeability factorHuman lung carcinoma cells
1997
Reversal of in vivo drug resistance by the transforming growth factor‐β inhibitor decorin
Teicher B, Maehara Y, Kakeh Y, Ara G, Keyes S, Wong J, Herbst R. Reversal of in vivo drug resistance by the transforming growth factor‐β inhibitor decorin. International Journal Of Cancer 1997, 71: 49-58. PMID: 9096665, DOI: 10.1002/(sici)1097-0215(19970328)71:1<49::aid-ijc10>3.0.co;2-4.Peer-Reviewed Original ResearchConceptsEMT-6/CDDP tumorTumor cell survivalParent tumorResistant tumorsDrug resistanceAdministration of decorinCell survivalEMT-6/CTXPlasma TGF-beta levelsTGF-beta proteinGranulocyte-macrophage colony-stimulating factorSitu hybridizationTGF-beta levelsVivo drug resistanceHigher plasma levelsTGF-beta mRNATumor-bearing animalsMurine mammary tumorsGrowth factorColony-stimulating factorDrug responseDecorinCytotoxic therapyPlasma levelsTumor levels