2024
Precision needle-punch tumor enrichment from paraffin blocks improves the detection of clinically actionable genomic alterations and biomarkers
Lin D, Huang R, Ladas I, Keller R, Patel N, Lakis S, Decker B, Janovitz T, Mata D, Ross J, Vergilio J, Elvin J, Herbst R, Mack P, Killian J. Precision needle-punch tumor enrichment from paraffin blocks improves the detection of clinically actionable genomic alterations and biomarkers. Frontiers In Oncology 2024, 14: 1328512. PMID: 38444675, PMCID: PMC10912171, DOI: 10.3389/fonc.2024.1328512.Peer-Reviewed Original ResearchTumor mutational burdenTumor purityTumor specimensNext-generation sequencingClinically actionable genomic alterationsMicrosatellite instabilityBiomarker statusTissue-conserving methodTissue blocksHigh tumor purityLow tumor purityComplex biomarkersSurgical pathology materialClinical samplesClinical trial enrollmentVariant allele frequencyResidual tumorMutational burdenTumor enrichmentTumor contentTumor cellsGenomic alterationsFormalin-fixedParaffin blocksDetect mutations
2020
Increased tumor purity and improved biomarker detection using precision needle punch enrichment of pathology specimen paraffin blocks: Method validation and implementation in a prospective clinical trial.
Killian J, Wright C, Chan L, Danziger N, Elvin J, Vergilio J, Lin D, Williams E, Ramkissoon S, Severson E, Hemmerich A, Duncan D, Edgerly C, Tse J, McGregor K, Schrock A, Alexander B, Ross J, Redman M, Herbst R. Increased tumor purity and improved biomarker detection using precision needle punch enrichment of pathology specimen paraffin blocks: Method validation and implementation in a prospective clinical trial. Journal Of Clinical Oncology 2020, 38: 3622-3622. DOI: 10.1200/jco.2020.38.15_suppl.3622.Peer-Reviewed Original ResearchProspective clinical trialsClinical trialsTumor purityTissue blocksClinical trial enrollmentHomologous recombination deficiency scoresValidation studyTrial enrollmentTrial armsHigh tumor purityPathology specimensShort variantDeficiency scoresParaffin blocksPatient matchingTumor cellsBiomarker resultsStatistical differenceComplex biomarkersPass/fail rateSequencing assaysTrialsGenomic lossScoresGroupImmune Cell PD-L1 Colocalizes with Macrophages and Is Associated with Outcome in PD-1 Pathway Blockade Therapy
Liu Y, Zugazagoitia J, Ahmed FS, Henick BS, Gettinger S, Herbst RS, Schalper KA, Rimm DL. Immune Cell PD-L1 Colocalizes with Macrophages and Is Associated with Outcome in PD-1 Pathway Blockade Therapy. Clinical Cancer Research 2020, 26: 970-977. PMID: 31615933, PMCID: PMC7024671, DOI: 10.1158/1078-0432.ccr-19-1040.Peer-Reviewed Original ResearchConceptsPD-L1 expressionHigh PD-L1 expressionPD-L1 levelsPD-L1Immune cellsTumor cellsT cellsHigh PD-L1 levelsPredominant immune cell typeNon-small cell lung cancer (NSCLC) casesDifferent immune cell subsetsCell lung cancer casesElevated PD-L1High PD-L1Better overall survivalDeath ligand 1Natural killer cellsImmune cell subsetsMultiple immune cellsCytotoxic T cellsLung cancer casesImmune cell typesCD68 levelsCell typesBlockade therapy
2019
Quantitative Assessment of CMTM6 in the Tumor Microenvironment and Association with Response to PD-1 Pathway Blockade in Advanced-Stage Non–Small Cell Lung Cancer
Zugazagoitia J, Liu Y, Toki M, McGuire J, Ahmed FS, Henick BS, Gupta R, Gettinger S, Herbst R, Schalper KA, Rimm DL. Quantitative Assessment of CMTM6 in the Tumor Microenvironment and Association with Response to PD-1 Pathway Blockade in Advanced-Stage Non–Small Cell Lung Cancer. Journal Of Thoracic Oncology 2019, 14: 2084-2096. PMID: 31605795, PMCID: PMC6951804, DOI: 10.1016/j.jtho.2019.09.014.Peer-Reviewed Original ResearchConceptsPD-L1CMTM6 expressionPathway blockadeAdvanced stage non-small cell lung cancerNon-small cell lung cancerPD-1 pathway blockadeTumor cellsAbsence of immunotherapyMultiplexed quantitative immunofluorescencePD-L1 coexpressionStromal immune cellsPD-L1 expressionT cell infiltrationLonger overall survivalCell lung cancerIndependent retrospective cohortsKRAS mutational statusExpression of CMTM6MARVEL transmembrane domainNSCLC cohortOverall survivalRetrospective cohortAxis blockadeClinical featuresImmunotherapy outcomes
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
2016
Immune checkpoint therapy for non-small-cell lung cancer: an update
Xia B, Herbst RS. Immune checkpoint therapy for non-small-cell lung cancer: an update. Immunotherapy 2016, 8: 279-298. PMID: 26860624, DOI: 10.2217/imt.15.123.Peer-Reviewed Original ResearchConceptsCell lung cancerImmune checkpointsLung cancerCo-inhibitory immune checkpointsRole of immunotherapyImmune checkpoint therapyImmune checkpoint pathwaysSynergistic antitumor activityCheckpoint inhibitorsInhibitory checkpointsCheckpoint therapyL1 antibodyImmune cellsNovel therapiesImmune activityAntagonist antibodyTumor growthTumor microenvironmentTumor cellsTherapyAntitumor activityAntibodiesCancerImmunotherapyCells
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 system
2013
CXCR2 Expression in Tumor Cells Is a Poor Prognostic Factor and Promotes Invasion and Metastasis in Lung Adenocarcinoma
Saintigny P, Massarelli E, Lin S, Ahn YH, Chen Y, Goswami S, Erez B, O'Reilly MS, Liu D, Lee JJ, Zhang L, Ping Y, Behrens C, Soto L, Heymach JV, Kim ES, Herbst RS, Lippman SM, Wistuba II, Hong WK, Kurie JM, Koo JS. CXCR2 Expression in Tumor Cells Is a Poor Prognostic Factor and Promotes Invasion and Metastasis in Lung Adenocarcinoma. Cancer Research 2013, 73: 571-582. PMID: 23204236, PMCID: PMC3548940, DOI: 10.1158/0008-5472.can-12-0263.Peer-Reviewed Original ResearchConceptsGene expression profilesNon-small cell lung cancerKnockdown clonesNSCLC cell linesHuman NSCLC cell linesExpression profilesCell linesStable knockdown clonesLung adenocarcinomaLung adenocarcinoma cell linesTumor cellsRAS pathway activationCXCR2 expressionPoor prognosisLung cancer cellsOrthotopic syngeneic mouse modelAdenocarcinoma cell linePromotes InvasionExpression of CXCL5Role of CXCR2Poor prognostic factorCell lung cancerPromoter methylationSyngeneic mouse modelProtein expression
2011
Upregulated stromal EGFR and vascular remodeling in mouse xenograft models of angiogenesis inhibitor–resistant human lung adenocarcinoma
Cascone T, Herynk MH, Xu L, Du Z, Kadara H, Nilsson MB, Oborn CJ, Park YY, Erez B, Jacoby JJ, Lee JS, Lin HY, Ciardiello F, Herbst RS, Langley RR, Heymach JV. Upregulated stromal EGFR and vascular remodeling in mouse xenograft models of angiogenesis inhibitor–resistant human lung adenocarcinoma. Journal Of Clinical Investigation 2011, 121: 1313-1328. PMID: 21436589, PMCID: PMC3070607, DOI: 10.1172/jci42405.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAngiogenesis InhibitorsAnimalsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedApoptosisBevacizumabCell Line, TumorDrug Resistance, NeoplasmErbB ReceptorsGene Expression ProfilingHumansLung NeoplasmsMaleMiceMice, NudeNeovascularization, PathologicRNA, MessengerRNA, NeoplasmStromal CellsUp-RegulationVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2Xenograft Model Antitumor AssaysConceptsMouse xenograft modelHuman lung adenocarcinomaTumor cellsPrimary resistanceLung adenocarcinomaXenograft modelFGFR pathwayProgression-free survivalVEGF inhibitor bevacizumabEndothelium of tumorsInhibitors of angiogenesisCombination regimensTreatment of cancerVEGF inhibitorsPericyte coverageAntiangiogenic therapyVascular remodelingAngiogenesis inhibitorsTherapeutic efficacyTumor growthStromal pathwaysClinical useEGFRAcquired ResistanceEGFR pathway
2008
To kill a tumor cell: the potential of proapoptotic receptor agonists
Ashkenazi A, Herbst RS. To kill a tumor cell: the potential of proapoptotic receptor agonists. Journal Of Clinical Investigation 2008, 118: 1979-1990. PMID: 18523647, PMCID: PMC2396896, DOI: 10.1172/jci34359.Peer-Reviewed Original ResearchConceptsProapoptotic receptor agonistsApo2L/TRAILReceptor agonistRecombinant human Apo2L/TRAILExtrinsic apoptosis pathwayPotential therapeutic interventionsNovel molecular biomarkersApoptosis pathwayAgonistic mAbConventional therapyPreclinical dataTherapeutic interventionsTumor cellsMolecular biomarkersAbnormal cellsLogical targetTherapyAgonistsCellsExciting opportunitiesTumorigenesisPatientsApoptosisPathway
2007
Expression of epidermal growth factor (EGF)/transforming growth factor-α by human lung cancer cells determines their response to EGF receptor tyrosine kinase inhibition in the lungs of mice
Wu W, O'Reilly MS, Langley RR, Tsan RZ, Baker CH, Bekele N, Tang XM, Onn A, Fidler IJ, Herbst RS. Expression of epidermal growth factor (EGF)/transforming growth factor-α by human lung cancer cells determines their response to EGF receptor tyrosine kinase inhibition in the lungs of mice. Molecular Cancer Therapeutics 2007, 6: 2652-2663. PMID: 17913856, DOI: 10.1158/1535-7163.mct-06-0759.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAnimalsAntineoplastic AgentsBlotting, WesternCell ProliferationEpidermal Growth FactorErbB ReceptorsGefitinibGene DosageHumansLung NeoplasmsMaleMiceMice, NudePhosphorylationPurinesQuinazolinesReverse Transcriptase Polymerase Chain ReactionTransforming Growth Factor alphaXenograft Model Antitumor AssaysConceptsTumor-associated endothelial cellsEpidermal growth factor receptorTreatment of miceLung cancerEpidermal growth factorNCI-H441Endothelial cellsLung tumorsLigand expressionNon-small cell lung cancerExpression of EGFTumor cellsEGFR tyrosine kinase inhibitorsEGFR tyrosine kinase inhibitor gefitinibGrowth factorReceptor tyrosine kinase inhibitionTyrosine kinase inhibitor gefitinibLymph node metastasisCell lung cancerEGF receptor tyrosine kinase inhibitionLungs of miceHuman lung cancer cellsHuman lung cancerPrimary tumor growthTyrosine kinase inhibitors
2004
Quantitative Analysis of Biomarkers Defines an Optimal Biological Dose for Recombinant Human Endostatin in Primary Human Tumors
Davis DW, Shen Y, Mullani NA, Wen S, Herbst RS, O’Reilly M, Abbruzzese JL, McConkey DJ. Quantitative Analysis of Biomarkers Defines an Optimal Biological Dose for Recombinant Human Endostatin in Primary Human Tumors. Clinical Cancer Research 2004, 10: 33-42. PMID: 14734449, DOI: 10.1158/1078-0432.ccr-0736-3.Peer-Reviewed Original ResearchMeSH KeywordsAngiogenesis InhibitorsApoptosisBiomarkersCohort StudiesDiagnostic ImagingDose-Response Relationship, DrugEndostatinsEndothelial CellsHumansHypoxia-Inducible Factor 1, alpha SubunitIn Situ Nick-End LabelingNeoplasmsNeovascularization, PathologicPlatelet Endothelial Cell Adhesion Molecule-1Proto-Oncogene Proteins c-bcl-2Recombinant ProteinsTomography, Emission-ComputedTranscription FactorsConceptsHypoxia-inducible factor-1alphaRecombinant human endostatinMicrovessel densityLaser scanning cytometryTC deathHuman endostatinPhase I dose-finding studyTerminal deoxynucleotidyl transferase-mediated nick end labeling stainingTumor cellsEndothelial cellsTumor-associated endothelial cellsSignificant clinical activityFactor-1alphaRefractory solid tumorsCohort of patientsNick end labeling stainingPhase I trialDose-finding studyTumor microvessel densityTumor blood flowOptimal biological doseEnd labeling stainingWhole tissue sectionsPositron emission tomographyPrimary human tumors
1998
Paclitaxel/carboplatin administration along with antiangiogenic therapy in non-small-cell lung and breast carcinoma models
Herbst R, Takeuchi H, Teicher B. Paclitaxel/carboplatin administration along with antiangiogenic therapy in non-small-cell lung and breast carcinoma models. Cancer Chemotherapy And Pharmacology 1998, 41: 497-504. PMID: 9554595, DOI: 10.1007/s002800050773.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic Combined Chemotherapy ProtocolsBone Marrow CellsCarboplatinCarcinoma, Lewis LungCell SurvivalColony-Forming Units AssayCyclohexanesDrug SynergismDrug Therapy, CombinationFemaleMaleMammary Neoplasms, ExperimentalMiceMice, Inbred BALB CMice, Inbred C57BLMinocyclineNeovascularization, PathologicO-(Chloroacetylcarbamoyl)fumagillolPaclitaxelSesquiterpenesConceptsTNP-470/minocyclineEMT-6 mammary carcinomaBone marrow CFU-GMLewis lung carcinomaMarrow CFU-GMEMT-6 tumor cellsLung carcinomaMammary carcinomaCFU-GMNormal tissuesTumor cellsHigh-dose paclitaxelCell lung cancerCombination of paclitaxelToxicity of carboplatinEfficacy of chemotherapyTumor growth delayBreast carcinoma modelCytotoxicity of carboplatinEarly time pointsAgent regimenAntiangiogenic regimenCarboplatin administrationLung metastasesCell lung