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 density
2014
Vandetanib and Indwelling Pleural Catheter for Non–Small-Cell Lung Cancer With Recurrent Malignant Pleural Effusion
Massarelli E, Onn A, Marom EM, Alden CM, Liu DD, Tran HT, Mino B, Wistuba II, Faiz SA, Bashoura L, Eapen GA, Morice RC, Lee J, Hong WK, Herbst RS, Jimenez CA. Vandetanib and Indwelling Pleural Catheter for Non–Small-Cell Lung Cancer With Recurrent Malignant Pleural Effusion. Clinical Lung Cancer 2014, 15: 379-386. PMID: 24913066, PMCID: PMC4160385, DOI: 10.1016/j.cllc.2014.04.002.Peer-Reviewed Original ResearchConceptsRecurrent malignant pleural effusionCell lung cancer patientsMalignant pleural effusionLung cancer patientsCell lung cancerPleural effusionCancer patientsMedian timeCatheter placementLung cancerEastern Cooperative Oncology Group performance statusPoor overall median survivalEnd pointSingle-arm phase II clinical trialPhase II clinical trialIndwelling pleural catheterOverall median survivalPrimary end pointSecondary end pointsDaily oral doseWeeks of treatmentPleural fluid cytologyVEGF receptor inhibitorPleural fluid cytokinesEligible patients
2012
Multitargeted Tyrosine Kinase Inhibitors in Unselected Patients With Advanced Non–Small-Cell Lung Cancer (NSCLC): Impressions From MONET (the Motesanib NSCLC Efficacy and Tolerability Study)
Morgensztern D, Herbst RS. Multitargeted Tyrosine Kinase Inhibitors in Unselected Patients With Advanced Non–Small-Cell Lung Cancer (NSCLC): Impressions From MONET (the Motesanib NSCLC Efficacy and Tolerability Study). Journal Of Clinical Oncology 2012, 30: 2805-2808. PMID: 22753916, DOI: 10.1200/jco.2012.42.7260.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Non-Small-Cell LungFemaleHumansIndolesLung NeoplasmsMaleNiacinamideOligonucleotidesReceptors, Vascular Endothelial Growth FactorCombined MEK and VEGFR Inhibition in Orthotopic Human Lung Cancer Models Results in Enhanced Inhibition of Tumor Angiogenesis, Growth, and Metastasis
Takahashi O, Komaki R, Smith PD, Jürgensmeier JM, Ryan A, Bekele BN, Wistuba II, Jacoby JJ, Korshunova MV, Biernacka A, Erez B, Hosho K, Herbst RS, O'Reilly MS. Combined MEK and VEGFR Inhibition in Orthotopic Human Lung Cancer Models Results in Enhanced Inhibition of Tumor Angiogenesis, Growth, and Metastasis. Clinical Cancer Research 2012, 18: 1641-1654. PMID: 22275507, PMCID: PMC3306446, DOI: 10.1158/1078-0432.ccr-11-2324.Peer-Reviewed Original ResearchMeSH KeywordsAngiogenesis InhibitorsAnimalsAntineoplastic Combined Chemotherapy ProtocolsBenzimidazolesCarcinoma, Non-Small-Cell LungCell Line, TumorCell ProliferationDisease ProgressionHumansLung NeoplasmsMaleMiceMice, NudeMitogen-Activated Protein KinasesMolecular Targeted TherapyNeovascularization, PathologicPaclitaxelProto-Oncogene ProteinsProto-Oncogene Proteins p21(ras)QuinazolinesRas ProteinsReceptors, Vascular Endothelial Growth FactorXenograft Model Antitumor AssaysConceptsSignal-regulated kinase kinaseTumor cell proliferationCell proliferationReceptor tyrosine kinasesKinase kinaseAvailable MEK1/2 inhibitorHuman NSCLC cellsTyrosine kinaseVEGF receptor tyrosine kinasesERK phosphorylationNCI-H441MEK1/2 inhibitorApoptotic effectsAdjacent normal tissuesKinaseNSCLC cellsMEK inhibitionAntiangiogenic effectsSignalingOrthotopic human lung cancer modelAvailable potent inhibitorLung tumor growthPotent inhibitorTumor angiogenesisSelumetinibTargeting Vascular Endothelial Growth Factor in Patients With Squamous Cell Lung Cancer
Koo PJ, Morgensztern D, Boyer JL, Herbst RS. Targeting Vascular Endothelial Growth Factor in Patients With Squamous Cell Lung Cancer. Journal Of Clinical Oncology 2012, 30: 1137-1139. PMID: 22355057, DOI: 10.1200/jco.2011.40.4053.Peer-Reviewed Original ResearchAdenocarcinomaAdenocarcinoma of LungAngiogenesis InhibitorsBiomarkers, TumorCarcinoma, Squamous CellGene Expression Regulation, NeoplasticHemorrhageHumansLung NeoplasmsNeoplasm StagingPredictive Value of TestsPrognosisReceptors, Vascular Endothelial Growth FactorSignal TransductionTreatment OutcomeVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-1Vascular Endothelial Growth Factor Receptor-2Vascular Endothelial Growth Factor Receptor-3
2010
A Multicenter, Phase 2 Study of Vascular Endothelial Growth Factor Trap (Aflibercept) in Platinum- and Erlotinib-Resistant Adenocarcinoma of the Lung
Leighl NB, Raez LE, Besse B, Rosen PJ, Barlesi F, Massarelli E, Gabrail N, Hart LL, Albain KS, Berkowitz L, Melnyk O, Shepherd FA, Sternas L, Ackerman J, Shun Z, Miller VA, Herbst RS. A Multicenter, Phase 2 Study of Vascular Endothelial Growth Factor Trap (Aflibercept) in Platinum- and Erlotinib-Resistant Adenocarcinoma of the Lung. Journal Of Thoracic Oncology 2010, 5: 1054-1059. PMID: 20593550, DOI: 10.1097/jto.0b013e3181e2f7fb.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdultAgedAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Non-Small-Cell LungDrug Resistance, NeoplasmErlotinib HydrochlorideFemaleHumansLung NeoplasmsMaleMiddle AgedOrganoplatinum CompoundsQuinazolinesReceptors, Vascular Endothelial Growth FactorRecombinant Fusion ProteinsSalvage TherapySurvival RateTreatment OutcomeConceptsProgression-free survivalLung adenocarcinomaLung cancerResponse rateCommon grade 3/4 toxicitiesMedian progression-free survivalVascular endothelial growth factor trapGrade 5 hemoptysisReversible posterior leukoencephalopathyGrade 3/4 toxicitiesPrimary end pointPhase 2 studyPhase I trialSingle-agent activityDuration of responseOverall response ratePlacental growth factorCardiac ejection fractionProgression of diseaseActivity of VEGFIntravenous afliberceptPosterior leukoencephalopathyIntolerable toxicityOverall survivalCerebral ischemia
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
2007
Targeted Therapy Against VEGFR and EGFR With ZD6474 Enhances the Therapeutic Efficacy of Irradiation in an Orthotopic Model of Human Non–Small-Cell Lung Cancer
Shibuya K, Komaki R, Shintani T, Itasaka S, Ryan A, Jürgensmeier JM, Milas L, Ang K, Herbst RS, O'Reilly MS. Targeted Therapy Against VEGFR and EGFR With ZD6474 Enhances the Therapeutic Efficacy of Irradiation in an Orthotopic Model of Human Non–Small-Cell Lung Cancer. International Journal Of Radiation Oncology • Biology • Physics 2007, 69: 1534-1543. PMID: 17889445, PMCID: PMC2151850, DOI: 10.1016/j.ijrobp.2007.07.2350.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Line, TumorCell ProliferationCombined Modality TherapyDNA RepairEpidermal Growth FactorErbB ReceptorsFeasibility StudiesHumansLung NeoplasmsMaleMiceMice, NudeNeovascularization, PathologicPiperidinesPleural EffusionQuinazolinesRadiation ToleranceRadiation-Sensitizing AgentsReceptors, Vascular Endothelial Growth FactorVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2Xenograft Model Antitumor AssaysConceptsVascular endothelial growth factor receptor 2Epidermal growth factor receptorLung cancerHuman lung cancerOrthotopic modelRadiation therapyHuman lung adenocarcinoma cellsLung adenocarcinoma cellsConventional therapyAntitumor effectsOrthotopic human lung cancer modelNon-small cell lung cancerHuman non-small cell lung cancerHuman lung cancer modelAdenocarcinoma cellsGrowth factor receptor 2Lung tumor burdenLung cancer modelEndothelial growth factor receptor 2Pleural effusion formationFactor receptor 2Basic fibroblast growth factorMatrix metalloproteinase-2Human lung adenocarcinomaSublethal damage repair
2005
Role of novel targeted therapies in the clinic
Herbst RS. Role of novel targeted therapies in the clinic. British Journal Of Cancer 2005, 92: s21-s27. PMID: 15928655, PMCID: PMC2362061, DOI: 10.1038/sj.bjc.6602605.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalAntineoplastic AgentsClinical Trials as TopicErbB ReceptorsHumansNeoplasmsNeovascularization, PathologicPatient SelectionReceptors, Vascular Endothelial Growth FactorCurrent Management of Advanced Non-Small Cell Lung Cancer: Targeted Therapy
Isobe T, Herbst RS, Onn A. Current Management of Advanced Non-Small Cell Lung Cancer: Targeted Therapy. Seminars In Oncology 2005, 32: 315-328. PMID: 15988686, DOI: 10.1053/j.seminoncol.2005.02.016.Peer-Reviewed Original ResearchMeSH KeywordsAlkyl and Aryl TransferasesAngiogenesis InhibitorsAnimalsAntibodies, MonoclonalAntineoplastic AgentsCarcinoma, Non-Small-Cell LungCyclooxygenase InhibitorsDrug Delivery SystemsErbB ReceptorsFarnesyltranstransferaseHumansLung NeoplasmsMatrix Metalloproteinase InhibitorsProtein Kinase CReceptor, ErbB-2Receptors, Vascular Endothelial Growth FactorRetinoid X ReceptorsConceptsNon-small cell lung cancerAdvanced non-small cell lung cancerCell lung cancerLung cancerVascular endothelial growth factorEpidermal growth factor receptorBiological therapyGrowth factorLung cancer patientsCancer-related deathLung cancer progressionClinical study designNew therapeutic strategiesEndothelial growth factorGrowth factor receptorOverall prognosisPatient survivalStandard treatmentCancer patientsConventional chemotherapyFrequent causeRadiation therapyTherapeutic approachesAnticancer arsenalTherapeutic strategies
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
Angiogenesis inhibitors in lung cancer
Kim ES, Herbst RS. Angiogenesis inhibitors in lung cancer. Current Oncology Reports 2002, 4: 325-333. PMID: 12044242, DOI: 10.1007/s11912-002-0008-0.Peer-Reviewed Original ResearchMeSH KeywordsAngiogenesis InhibitorsAngiostatinsCarcinoma, Non-Small-Cell LungCollagenCyclohexanesEndostatinsHumansLung NeoplasmsO-(Chloroacetylcarbamoyl)fumagillolPeptide FragmentsPlasminogenReceptor Protein-Tyrosine KinasesReceptors, Growth FactorReceptors, Vascular Endothelial Growth FactorSesquiterpenesSurvival RateThalidomideConceptsLung cancerAngiogenesis inhibitorsSurvival rateMajor public health problemVascular endothelial growth factor receptorOngoing randomized studiesCell lung cancerEndothelial growth factor receptorTraditional cytotoxic therapiesCancer-related deathImproved survival ratesPublic health problemSevere side effectsInhibitors of angiogenesisEndogenous angiogenesis inhibitorGrowth factor receptorMetastatic diseaseRandomized studyChemotherapy dosesClinical benefitCytotoxic therapyCyclooxygenase inhibitorRadiation therapySide effectsHealth problems
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