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
2010
Phase I Dose-Escalation Study of Recombinant Human Apo2L/TRAIL, a Dual Proapoptotic Receptor Agonist, in Patients With Advanced Cancer
Herbst RS, Eckhardt SG, Kurzrock R, Ebbinghaus S, O'Dwyer PJ, Gordon MS, Novotny W, Goldwasser MA, Tohnya TM, Lum BL, Ashkenazi A, Jubb AM, Mendelson DS. Phase I Dose-Escalation Study of Recombinant Human Apo2L/TRAIL, a Dual Proapoptotic Receptor Agonist, in Patients With Advanced Cancer. Journal Of Clinical Oncology 2010, 28: 2839-2846. PMID: 20458040, DOI: 10.1200/jco.2009.25.1991.Peer-Reviewed Original ResearchConceptsRecombinant human Apo2L/TRAILRhApo2L/TRAILDose-escalation studyAdverse eventsAdvanced cancerLiver metastasesDose escalationLiver functionApo2L/TRAILI dose-escalation studyDurable partial responseRapid tumor necrosisAntitumor activityCommon adverse eventsLiver enzyme elevationMetastatic liver diseaseSerious adverse eventsAbnormal liver functionNormal liver functionMultiple intravenous dosesNecrosis factor-related apoptosis-inducing ligandPreclinical antitumor efficacyTumor necrosis factor-related apoptosis-inducing ligandFactor-related apoptosis-inducing ligandHuman clinical trials
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
2006
Antimetastatic activity of insulin-like growth factor binding protein-3 in lung cancer is mediated by insulin-like growth factor–independent urokinase-type plasminogen activator inhibition
Oh SH, Lee OH, Schroeder CP, Oh YW, Ke S, Cha HJ, Park RW, Onn A, Herbst RS, Li C, Lee HY. Antimetastatic activity of insulin-like growth factor binding protein-3 in lung cancer is mediated by insulin-like growth factor–independent urokinase-type plasminogen activator inhibition. Molecular Cancer Therapeutics 2006, 5: 2685-2695. PMID: 17121915, DOI: 10.1158/1535-7163.mct-06-0142.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsCell Line, TumorFemaleFibroblastsHumansInsulin-Like Growth Factor Binding Protein 3Lung NeoplasmsMatrix Metalloproteinase 2Matrix Metalloproteinase InhibitorsMiceMice, NudeNeoplasm MetastasisNIH 3T3 CellsReceptor, IGF Type 1Recombinant ProteinsSignal TransductionUrokinase-Type Plasminogen ActivatorConceptsNon-small cell lung cancerInsulin-like growth factorIGF-independent mechanismsIGFBP-3Recombinant IGFBP-3Expression/activityLung cancerNSCLC cellsMajor IGF-binding proteinProtein 3H1299 cellsLung cancer cell metastasisGrowth factorInvasion of H1299Experimental animal model systemsCell lung cancerIGF-binding proteinsLung cancer metastasisA549 NSCLC cellsMatrix metalloproteinase-2Anti-invasive activityHuman lung fibroblastsCancer cell metastasisAnimal model systemsPlasminogen activator inhibition
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
2003
In Vitro and In Vivo Assays for the Proliferative and Vascular Permeabilization Activities of Vascular Endothelial Growth Factor (VEGF) and Its Receptor
Yano S, Herbst RS, Sone S. In Vitro and In Vivo Assays for the Proliferative and Vascular Permeabilization Activities of Vascular Endothelial Growth Factor (VEGF) and Its Receptor. Methods In Molecular Medicine 2003, 74: 391-398. PMID: 12415710, DOI: 10.1385/1-59259-323-2:391.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCapillary PermeabilityCell DivisionCells, CulturedEndothelial Growth FactorsEndothelium, VascularHumansImmunoglobulin GIn Vitro TechniquesIntercellular Signaling Peptides and ProteinsLymphokinesMaleMiceMice, Inbred C57BLMice, NudeReceptors, Vascular Endothelial Growth FactorRecombinant ProteinsTetrazolium SaltsThiazolesThymidineVascular Endothelial Growth Factor AVascular Endothelial Growth FactorsConceptsNon-small cell lung cancerVascular endothelial growth factorLung cancerEarly-stage non-small cell lung cancerCell lung cancerNormal bronchial epitheliumEndothelial growth factorNew blood vesselsBronchial dysplasiaPoor prognosisPrimary tumorLung carcinogenesisMicrovascular densityBronchial epitheliumSolid tumorsBlood vesselsGrowth factorTumorsMetabolic demandsVivo assaysCancerEarly stagesCarcinomaPrognosisHyperplasia
2002
Development of biologic markers of response and assessment of antiangiogenic activity in a clinical trial of human recombinant endostatin.
Herbst RS, Mullani NA, Davis DW, Hess KR, McConkey DJ, Charnsangavej C, O’Reilly M, Kim HW, Baker C, Roach J, Ellis LM, Rashid A, Pluda J, Bucana C, Madden TL, Tran HT, Abbruzzese JL. Development of biologic markers of response and assessment of antiangiogenic activity in a clinical trial of human recombinant endostatin. Journal Of Clinical Oncology 2002, 20: 3804-14. PMID: 12228200, DOI: 10.1200/jco.2002.05.102.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdultAgedAngiogenesis InhibitorsApoptosisBiomarkersCD3 ComplexCollagenDose-Response Relationship, DrugEndostatinsEndotheliumFemaleFluorodeoxyglucose F18HumansIn Situ Nick-End LabelingLasersMaleMiddle AgedNeoplasmsNeovascularization, PathologicPeptide FragmentsProspective StudiesRecombinant ProteinsTomography, Emission-ComputedConceptsTumor blood flowRh-EndoTumor cell apoptosisPositron emission tomographyBlood flowEndothelial cell apoptosisCell apoptosisClinical trialsAntiangiogenic therapyEndothelial cellsWeeks of therapyStart of therapyDose-finding clinical trialsRecombinant human endostatinHuman recombinant endostatinTreatment of cancerBiologic markersAntiangiogenic treatmentBiopsy specimensAppropriate dosePET scansBiopsy analysisHuman endostatinTherapyTumor tissuePhase I study of recombinant human endostatin in patients with advanced solid tumors.
Herbst RS, Hess KR, Tran HT, Tseng JE, Mullani NA, Charnsangavej C, Madden T, Davis DW, McConkey DJ, O’Reilly M, Ellis LM, Pluda J, Hong WK, Abbruzzese JL. Phase I study of recombinant human endostatin in patients with advanced solid tumors. Journal Of Clinical Oncology 2002, 20: 3792-803. PMID: 12228199, DOI: 10.1200/jco.2002.11.061.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdultAgedAngiogenesis InhibitorsCollagenCollagen Type XVIIIEndostatinsEndothelial Growth FactorsE-SelectinFemaleFibroblast Growth Factor 2Hematologic DiseasesHumansImmunoglobulinsInfusions, IntravenousLymphokinesMagnetic Resonance ImagingMaleMaximum Tolerated DoseMiddle AgedNeoplasmsPeptide FragmentsRecombinant ProteinsTime FactorsTissue DistributionVascular Cell Adhesion Molecule-1Vascular Endothelial Growth Factor AVascular Endothelial Growth FactorsConceptsRh-EndoConcentration-time curveRecombinant human endostatinSerum markersPreclinical modelsSolid tumorsHuman endostatinDose-limiting toxic effectAntitumor activityTwo-compartmental open modelAdvanced solid tumorsPhase I trialCentral line accessDose-finding trialMinor antitumor activityI trialIntravenous bolusSerum biomarkersSerum antibodiesPharmacokinetic dispositionAllergic reactionsPatientsPharmacokinetic profileDose levelsPhase ITargeted therapy against human lung cancer in nude mice by high-affinity recombinant antimesothelin single-chain Fv immunotoxin.
Fan D, Yano S, Shinohara H, Solorzano C, Van Arsdall M, Bucana CD, Pathak S, Kruzel E, Herbst RS, Onn A, Roach JS, Onda M, Wang QC, Pastan I, Fidler IJ. Targeted therapy against human lung cancer in nude mice by high-affinity recombinant antimesothelin single-chain Fv immunotoxin. Molecular Cancer Therapeutics 2002, 1: 595-600. PMID: 12479219.Peer-Reviewed Original ResearchMeSH KeywordsADP Ribose TransferasesAnimalsBacterial ToxinsDose-Response Relationship, DrugExotoxinsFlow CytometryHumansImmunoglobulin FragmentsImmunotherapyKineticsLung NeoplasmsMesothelinMiceMice, NudeMicroscopy, FluorescenceMutationNeoplasm TransplantationPseudomonasRecombinant ProteinsTumor Cells, CulturedVirulence FactorsConceptsTargeted therapyNude miceHuman non-small cell lung cancer cellsNon-small cell lung cancer cellsNCI-H226 cellsHuman lung cancer cell linesCell lung cancer cellsSquamous cell carcinomaLung cancer cell linesHuman lung cancerExperimental lung metastasisLung cancer cellsPC14PE6 cellsCancer cell linesLung metastasesCell carcinomaCancer patientsLung cancerOvarian cancerNontoxic doseMesothelinDay 7Recombinant immunotoxinCertain cancersCancer
2001
Clinical studies of angiogenesis inhibitors: The university of texas md anderson center trial of human endostatin
Herbst R, Lee A, Tran H, Abbruzzese J. Clinical studies of angiogenesis inhibitors: The university of texas md anderson center trial of human endostatin. Current Oncology Reports 2001, 3: 131-140. PMID: 11177745, DOI: 10.1007/s11912-001-0013-8.Peer-Reviewed Original ResearchConceptsPhase I trialI trialClinical studiesHuman endostatinTumor vasculatureSolid tumor malignanciesAnti-angiogenic agentsAnti-angiogenic mechanismAnti-angiogenic compoundsToxic cancer treatmentsAdvanced diseaseBlood vessel supplyCenter trialMinimal diseaseTumor sizeNovel agentsSurrogate endpointsNew agentsSide effectsBiologic mechanismsSingle agentAngiogenesis inhibitorsGrowth-inhibiting moleculesNon-toxic agentsTumor growth