2016
KDR Amplification Is Associated with VEGF-Induced Activation of the mTOR and Invasion Pathways but does not Predict Clinical Benefit to the VEGFR TKI Vandetanib
Nilsson MB, Giri U, Gudikote J, Tang X, Lu W, Tran H, Fan Y, Koo A, Diao L, Tong P, Wang J, Herbst R, Johnson BE, Ryan A, Webster A, Rowe P, Wistuba II, Heymach JV. KDR Amplification Is Associated with VEGF-Induced Activation of the mTOR and Invasion Pathways but does not Predict Clinical Benefit to the VEGFR TKI Vandetanib. Clinical Cancer Research 2016, 22: 1940-1950. PMID: 26578684, PMCID: PMC4834253, DOI: 10.1158/1078-0432.ccr-15-1994.Peer-Reviewed Original ResearchMeSH KeywordsCarcinoma, Non-Small-Cell LungCell Line, TumorCell MovementCell ProliferationHumansHypoxia-Inducible Factor 1, alpha SubunitLung NeoplasmsP38 Mitogen-Activated Protein KinasesPiperidinesProtein Kinase InhibitorsProto-Oncogene Proteins c-metQuinazolinesSignal TransductionTOR Serine-Threonine KinasesTreatment OutcomeVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2ConceptsNon-small cell lung cancerTyrosine kinase inhibitorsVEGFR tyrosine kinase inhibitorsNSCLC cell linesZODIAC studyClinical benefitLung cancerPlatinum-refractory non-small cell lung cancerAdvanced non-small cell lung cancerImproved progression-free survivalDifferent lung cancersObjective response rateProgression-free survivalVEGF pathway inhibitorsCell lung cancerArchival tumor samplesCell linesActivation of mTORVandetanib armOverall survivalNSCLC modelsNSCLC cellsPreclinical studiesPatientsVEGFR inhibition
2012
Targeting 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
2011
Increased VEGFR-2 Gene Copy Is Associated with Chemoresistance and Shorter Survival in Patients with Non–Small-Cell Lung Carcinoma Who Receive Adjuvant Chemotherapy
Yang F, Tang X, Riquelme E, Behrens C, Nilsson MB, Giri U, Varella-Garcia M, Byers LA, Lin HY, Wang J, Raso MG, Girard L, Coombes K, Lee JJ, Herbst RS, Minna JD, Heymach JV, Wistuba II. Increased VEGFR-2 Gene Copy Is Associated with Chemoresistance and Shorter Survival in Patients with Non–Small-Cell Lung Carcinoma Who Receive Adjuvant Chemotherapy. Cancer Research 2011, 71: 5512-5521. PMID: 21724587, PMCID: PMC3159530, DOI: 10.1158/0008-5472.can-10-2614.Peer-Reviewed Original ResearchMeSH KeywordsCarcinoma, Non-Small-Cell LungChemotherapy, AdjuvantDrug Resistance, NeoplasmGene DosageHumansIn Situ Hybridization, FluorescenceLung NeoplasmsPolymerase Chain ReactionPolymorphism, Single NucleotideSurvival RateVascular Endothelial Growth Factor Receptor-2ConceptsCell lung carcinomaHIF-1α levelsAdjuvant therapyLung carcinomaAdjuvant platinum-based chemotherapyVEGFR-2 blockadeNuclear hypoxia inducible factor-1αNSCLC tumor cellsPlatinum-based chemotherapyFavorable overall survivalRisk of deathHypoxia-inducible factor-1αHigher microvessel densityNSCLC tumor specimensNSCLC cell linesInducible factor-1αCell linesVEGF receptor 2Adjuvant chemotherapyOverall survivalClinical outcomesAdenocarcinoma patientsMicrovessel densityShorter SurvivalHigh riskUpregulated 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
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 repairTargeted therapy of orthotopic human lung cancer by combined vascular endothelial growth factor and epidermal growth factor receptor signaling blockade
Wu W, Onn A, Isobe T, Itasaka S, Langley RR, Shitani T, Shibuya K, Komaki R, Ryan AJ, Fidler IJ, Herbst RS, O'Reilly MS. Targeted therapy of orthotopic human lung cancer by combined vascular endothelial growth factor and epidermal growth factor receptor signaling blockade. Molecular Cancer Therapeutics 2007, 6: 471-483. PMID: 17308046, DOI: 10.1158/1535-7163.mct-06-0416.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAngiogenesis InhibitorsAnimalsApoptosisBlotting, WesternCarcinoma, Squamous CellCell Line, TumorCell ProliferationEndothelium, VascularErbB ReceptorsFlow CytometryHumansLung NeoplasmsMaleMiceMice, Inbred BALB CMice, Inbred CBANeovascularization, PathologicPhosphorylationPiperidinesProto-Oncogene Proteins c-aktQuinazolinesSignal TransductionVascular Endothelial Growth Factor Receptor-2Xenograft Model Antitumor AssaysConceptsVascular endothelial growth factorVEGF receptor 2EGF receptorEpidermal growth factorLung cancerHuman lung cancerEndothelial growth factorGrowth factorMitogen-activated protein kinaseNon-small cell lung cancerOrthotopic human lung cancerProtein tyrosine kinase inhibitorEndothelial cellsTumor-associated endothelial cellsHuman lung cancer specimensAdvanced lung cancerSelective protein tyrosine kinase inhibitorCell lung cancerLung cancer patientsOrthotopic mouse modelEndothelial cell tube formationLung cancer specimensHuman lung adenocarcinoma cellsTyrosine kinase inhibitorsSmall molecule inhibitors
2005
Pharmacodynamic Analysis of Target Inhibition and Endothelial Cell Death in Tumors Treated with the Vascular Endothelial Growth Factor Receptor Antagonists SU5416 or SU6668
Davis DW, Takamori R, Raut CP, Xiong HQ, Herbst RS, Stadler WM, Heymach JV, Demetri GD, Rashid A, Shen Y, Wen S, Abbruzzese JL, McConkey DJ. Pharmacodynamic Analysis of Target Inhibition and Endothelial Cell Death in Tumors Treated with the Vascular Endothelial Growth Factor Receptor Antagonists SU5416 or SU6668. Clinical Cancer Research 2005, 11: 678-689. PMID: 15701856, DOI: 10.1158/1078-0432.678.11.2.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAnimalsApoptosisDose-Response Relationship, DrugEndothelium, VascularFemaleHumansIndolesMaleMiceMice, NudeMiddle AgedNeovascularization, PathologicOxindolesPancreatic NeoplasmsPhosphorylationPropionatesPyrrolesReceptor, Platelet-Derived Growth Factor betaTransplantation, HeterologousVascular Endothelial Growth Factor Receptor-2ConceptsPlatelet-derived growth factor receptorTumor microvessel densityGrowth factor receptorMicrovessel densityCell apoptosisVascular endothelial growth factor receptorAdvanced solid malignanciesFactor receptorEndothelial growth factor receptorPrimary patient tumorsG core biopsyDose-dependent effectPhosphorylated VEGFR-2Primary human tumorsEndothelial cell deathCell deathEndothelial cell apoptosisTumor cell apoptosisTumor cell deathPost therapyCore biopsyPharmacodynamic analysisSolid malignanciesVessel sizeClinical trials