Featured Publications
The end of the beginning: progress and next steps in KRAS-mutant non-small-cell lung cancer
Goldberg S, Herbst R. The end of the beginning: progress and next steps in KRAS-mutant non-small-cell lung cancer. The Lancet 2023, 401: 706-707. PMID: 36774937, DOI: 10.1016/s0140-6736(23)00288-x.Peer-Reviewed Original Research
2017
Impaired HLA Class I Antigen Processing and Presentation as a Mechanism of Acquired Resistance to Immune Checkpoint Inhibitors in Lung Cancer
Gettinger S, Choi J, Hastings K, Truini A, Datar I, Sowell R, Wurtz A, Dong W, Cai G, Melnick MA, Du VY, Schlessinger J, Goldberg SB, Chiang A, Sanmamed MF, Melero I, Agorreta J, Montuenga LM, Lifton R, Ferrone S, Kavathas P, Rimm DL, Kaech SM, Schalper K, Herbst RS, Politi K. Impaired HLA Class I Antigen Processing and Presentation as a Mechanism of Acquired Resistance to Immune Checkpoint Inhibitors in Lung Cancer. Cancer Discovery 2017, 7: cd-17-0593. PMID: 29025772, PMCID: PMC5718941, DOI: 10.1158/2159-8290.cd-17-0593.Peer-Reviewed Original ResearchMeSH KeywordsDrug Resistance, NeoplasmGene Expression Regulation, NeoplasticHistocompatibility Antigens Class IHumansLung NeoplasmsSignal TransductionConceptsImmune checkpoint inhibitorsPatient-derived xenograftsHLA class ILung cancerClass ICell surface HLA class ILung cancer mouse modelPD-1 blockadeStandard treatment algorithmCancer mouse modelLung cancer samplesDefective antigen processingCheckpoint inhibitorsPD-1Treatment algorithmMouse modelAntagonistic antibodiesDiverse malignanciesAntigen processingCancer samplesB2MHomozygous lossTumorsCancerRecurrent mutationsStress hormones promote EGFR inhibitor resistance in NSCLC: Implications for combinations with β-blockers
Nilsson MB, Sun H, Diao L, Tong P, Liu D, Li L, Fan Y, Poteete A, Lim SO, Howells K, Haddad V, Gomez D, Tran H, Pena GA, Sequist LV, Yang JC, Wang J, Kim ES, Herbst R, Lee JJ, Hong WK, Wistuba I, Hung MC, Sood AK, Heymach JV. Stress hormones promote EGFR inhibitor resistance in NSCLC: Implications for combinations with β-blockers. Science Translational Medicine 2017, 9 PMID: 29118262, PMCID: PMC5870120, DOI: 10.1126/scitranslmed.aao4307.Peer-Reviewed Original ResearchMeSH KeywordsAdrenergic beta-AntagonistsAfatinibAMP-Activated Protein Kinase KinasesCarcinoma, Non-Small-Cell LungCell Line, TumorCyclic AMP Response Element-Binding ProteinDrug Resistance, NeoplasmEpinephrineErbB ReceptorsHumansInterleukin-6Lung NeoplasmsMutationNorepinephrineProtein Kinase CProtein Kinase InhibitorsProtein Serine-Threonine KinasesQuinazolinesReceptors, Adrenergic, betaSignal TransductionXenograft Model Antitumor AssaysConceptsNon-small cell lung cancerEGFR inhibitor resistanceΒ-blockersInhibitor resistanceStress hormonesLiver kinase B1Epidermal growth factor receptor tyrosine kinase inhibitor resistanceLower IL-6 concentrationsΒ-blocker useIL-6 concentrationsIL-6 inhibitionCell lung cancerTyrosine kinase inhibitor resistanceEGFR-TKI resistanceInterleukin-6 expressionKinase inhibitor resistanceChronic stress hormonesNSCLC patientsEGFR-TKIIL-6Lung cancerAR activationWorse outcomesNSCLC cellsTKI resistanceJAK1/STAT3 Activation through a Proinflammatory Cytokine Pathway Leads to Resistance to Molecularly Targeted Therapy in Non–Small Cell Lung Cancer
Shien K, Papadimitrakopoulou VA, Ruder D, Behrens C, Shen L, Kalhor N, Song J, Lee JJ, Wang J, Tang X, Herbst RS, Toyooka S, Girard L, Minna JD, Kurie JM, Wistuba II, Izzo JG. JAK1/STAT3 Activation through a Proinflammatory Cytokine Pathway Leads to Resistance to Molecularly Targeted Therapy in Non–Small Cell Lung Cancer. Molecular Cancer Therapeutics 2017, 16: 2234-2245. PMID: 28729401, PMCID: PMC5628136, DOI: 10.1158/1535-7163.mct-17-0148.Peer-Reviewed Original ResearchMeSH KeywordsAgedApoptosisCancer-Associated FibroblastsCarcinoma, Non-Small-Cell LungCell Line, TumorCytokinesDrug Resistance, NeoplasmEpithelial-Mesenchymal TransitionFemaleGene Expression Regulation, NeoplasticHumansInterleukin-6Janus Kinase 1MaleMiddle AgedMolecular Targeted TherapyNeoplasm StagingOncostatin MReceptors, Oncostatin MSignal TransductionSTAT3 Transcription FactorConceptsNon-small cell lung cancerCancer-associated fibroblastsNSCLC cellsOSM receptorMajority of patientsCell lung cancerProinflammatory cytokine IL6Proinflammatory cytokine pathwaysSignificant therapeutic advancesClinical NSCLC samplesMol Cancer TherSTAT3-dependent mannerOSMR expressionDrug-induced apoptosisWorse prognosisPrognostic significanceLung cancerTherapeutic advancesCytokines IL6Molecule expressionNSCLC samplesCytokine pathwaysLung adenocarcinomaTargeted drugsParacrine mechanismsThe 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
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 inhibitionGSK-3α Is a Novel Target of CREB and CREB-GSK-3α Signaling Participates in Cell Viability in Lung Cancer
Park SA, Lee JW, Herbst RS, Koo JS. GSK-3α Is a Novel Target of CREB and CREB-GSK-3α Signaling Participates in Cell Viability in Lung Cancer. PLOS ONE 2016, 11: e0153075. PMID: 27049759, PMCID: PMC4822949, DOI: 10.1371/journal.pone.0153075.Peer-Reviewed Original Research
2015
Co-occurring Genomic Alterations Define Major Subsets of KRAS-Mutant Lung Adenocarcinoma with Distinct Biology, Immune Profiles, and Therapeutic Vulnerabilities
Skoulidis F, Byers LA, Diao L, Papadimitrakopoulou VA, Tong P, Izzo J, Behrens C, Kadara H, Parra ER, Canales JR, Zhang J, Giri U, Gudikote J, Cortez MA, Yang C, Fan Y, Peyton M, Girard L, Coombes KR, Toniatti C, Heffernan TP, Choi M, Frampton GM, Miller V, Weinstein JN, Herbst RS, Wong KK, Zhang J, Sharma P, Mills GB, Hong WK, Minna JD, Allison JP, Futreal A, Wang J, Wistuba II, Heymach JV. Co-occurring Genomic Alterations Define Major Subsets of KRAS-Mutant Lung Adenocarcinoma with Distinct Biology, Immune Profiles, and Therapeutic Vulnerabilities. Cancer Discovery 2015, 5: 860-877. PMID: 26069186, PMCID: PMC4527963, DOI: 10.1158/2159-8290.cd-14-1236.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdenocarcinoma of LungAMP-Activated Protein Kinase KinasesAMP-Activated Protein KinasesCell Line, TumorCluster AnalysisDNA-Binding ProteinsGene ExpressionGene Expression ProfilingGenetic VariationGenomicsHumansInflammationLung NeoplasmsMutationOxidative StressPrognosisProtein Serine-Threonine KinasesRas ProteinsSignal TransductionTranscription FactorsTumor Suppressor ProteinsConceptsKRAS-mutant lung adenocarcinomaCo-occurring genomic alterationsLung adenocarcinomaDistinct biologyTherapeutic vulnerabilitiesSTK11/LKB1Hsp90 inhibitor therapyRelapse-free survivalDrug sensitivity patternsGenomic alterationsCDKN2A/BKC tumorsInflammatory markersMucinous histologyImmune markersImmune profilePD-L1AdenocarcinomaSensitivity patternMajor subsetNKX2-1 transcription factorLow expressionTumorsGenetic alterationsEffector moleculesInnovative Clinical Trials: The LUNG‐MAP Study
Steuer C, Papadimitrakopoulou V, Herbst R, Redman M, Hirsch F, Mack P, Ramalingam S, Gandara. Innovative Clinical Trials: The LUNG‐MAP Study. Clinical Pharmacology & Therapeutics 2015, 97: 488-491. PMID: 25676724, DOI: 10.1002/cpt.88.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic AgentsBiomarkers, TumorCarcinoma, Non-Small-Cell LungCarcinoma, Squamous CellClinical Trials, Phase II as TopicClinical Trials, Phase III as TopicGenetic Predisposition to DiseaseGenomicsHumansLung NeoplasmsMolecular Targeted TherapyPhenotypePrecision MedicineResearch DesignSignal TransductionConceptsCell lung cancerSquamous cell carcinomaSquamous cell lung cancerCell carcinomaLung cancerTrial designNon-small cell lung cancerMetastatic squamous cell carcinomaSecond-line therapyProportion of patientsNew active drugsNovel trial designsDrug developmentWide molecular heterogeneityAdenocarcinoma histologyLine therapyTherapeutic optionsLung-MAPClinical trialsGroup trialsActive drugPatientsMaster protocolsCarcinomaCancer
2014
Emerging Science and Therapies in Non-small-Cell Lung Cancer: Targeting the MET Pathway
Kris MG, Arenberg DA, Herbst RS, Riely GJ. Emerging Science and Therapies in Non-small-Cell Lung Cancer: Targeting the MET Pathway. Clinical Lung Cancer 2014, 15: 475. PMID: 25306384, DOI: 10.1016/j.cllc.2014.08.001.Peer-Reviewed Original ResearchConceptsCell lung cancerLung cancerMET pathwayNon-small cell lung cancerCME activitiesProgression-free survivalLung cancer patientsLung cancer specialistsCare of patientsIndividualized treatment strategiesLung cancer mutationsClinical research advancesQuality of lifeCollection of diseasesFree survivalMedical oncologistsCancer patientsCancer specialistsPatient outcomesTreatment strategiesHealthcare cliniciansCancer cell mutationsPatientsTissue acquisitionMET expressionA RAS Renaissance: Emerging Targeted Therapies for KRAS-Mutated Non–Small Cell Lung Cancer
Vasan N, Boyer JL, Herbst RS. A RAS Renaissance: Emerging Targeted Therapies for KRAS-Mutated Non–Small Cell Lung Cancer. Clinical Cancer Research 2014, 20: 3921-3930. PMID: 24893629, PMCID: PMC5369356, DOI: 10.1158/1078-0432.ccr-13-1762.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerCell lung cancerLung cancerClinical trialsNew clinical trialsEarly clinical trialsPathway-targeted therapiesTargeted therapyMechanism of activityNovel targetCancerDruggable targetsTherapyDisappointing resultsHuman cancersSmall-molecule screenFarnesyltransferase inhibitorsRAS gene productsNew RATrialsPharmaceutical companiesNumerous oncogenesNumerous studiesSynthetic lethality screenPathway
2013
Caspase-Independent Cell Death Is Involved in the Negative Effect of EGF Receptor Inhibitors on Cisplatin in Non–Small Cell Lung Cancer Cells
Yamaguchi H, Hsu JL, Chen CT, Wang YN, Hsu MC, Chang SS, Du Y, Ko HW, Herbst R, Hung MC. Caspase-Independent Cell Death Is Involved in the Negative Effect of EGF Receptor Inhibitors on Cisplatin in Non–Small Cell Lung Cancer Cells. Clinical Cancer Research 2013, 19: 845-854. PMID: 23344263, PMCID: PMC3703145, DOI: 10.1158/1078-0432.ccr-12-2621.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Non-Small-Cell LungCaspasesCell DeathCell Line, TumorCisplatinDrug Resistance, NeoplasmEpidermal Growth FactorErbB ReceptorsForkhead Box Protein O3Forkhead Transcription FactorsGefitinibHumansProtein Kinase InhibitorsQuinazolinesSignal TransductionConceptsCaspase-independent cell deathTyrosine kinase inhibitorsSuberoylanilide hydroxamic acidReactive oxygen speciesLung cancerCell deathEGFR cellsEffects of TKIsNon-small cell lung cancer cellsCaspase-dependent apoptotic cell deathCisplatin-induced reactive oxygen speciesReceptor tyrosine kinase inhibitorsInducer of ROSCell lung cancer cellsPlatinum-based chemotherapyEGF receptor tyrosine kinase inhibitorMultiple clinical trialsEfficacy of chemotherapyEfficacy of cisplatinEffect of cisplatinLung cancer cellsApoptotic cell deathWild-type EGFREGF receptor inhibitorClinical trials
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-2DulanerminLungTumorsTargeting 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-3Effect of KRAS Oncogene Substitutions on Protein Behavior: Implications for Signaling and Clinical Outcome
Ihle NT, Byers LA, Kim ES, Saintigny P, Lee JJ, Blumenschein GR, Tsao A, Liu S, Larsen JE, Wang J, Diao L, Coombes KR, Chen L, Zhang S, Abdelmelek MF, Tang X, Papadimitrakopoulou V, Minna JD, Lippman SM, Hong WK, Herbst RS, Wistuba II, Heymach JV, Powis G. Effect of KRAS Oncogene Substitutions on Protein Behavior: Implications for Signaling and Clinical Outcome. Journal Of The National Cancer Institute 2012, 104: 228-239. PMID: 22247021, PMCID: PMC3274509, DOI: 10.1093/jnci/djr523.Peer-Reviewed Original ResearchMeSH KeywordsAspartic AcidCarcinoma, Non-Small-Cell LungCell Line, TumorClinical Trials, Phase II as TopicCysteineDisease-Free SurvivalGene Expression ProfilingGene Expression Regulation, NeoplasticGenes, rasGenetic VectorsGlycineHumansImmunoblottingImmunoprecipitationKaplan-Meier EstimateLentivirusLung NeoplasmsMicroarray AnalysisMolecular Targeted TherapyMutationProto-Oncogene Proteins c-aktRandomized Controlled Trials as TopicSignal TransductionTOR Serine-Threonine KinasesTreatment OutcomeValineConceptsNon-small cell lung cancerKirsten rat sarcoma viral oncogene homologProgression-free survivalNSCLC cell linesWild-type KrasMutant KrasRefractory non-small cell lung cancerWorse progression-free survivalRat sarcoma viral oncogene homologRas2 Kirsten rat sarcoma viral oncogene homologSarcoma viral oncogene homologKaplan-Meier curvesCell lung cancerReverse-phase protein array studiesKRas proteinsHuman bronchial epithelial cellsCancer cell growthPatient tumor samplesCell linesImmortalized human bronchial epithelial cellsBronchial epithelial cellsProtein array studiesTumor gene expressionEvaluable patientsClinical outcomes
2010
Combination Treatment with MEK and AKT Inhibitors Is More Effective than Each Drug Alone in Human Non-Small Cell Lung Cancer In Vitro and In Vivo
Meng J, Dai B, Fang B, Bekele BN, Bornmann WG, Sun D, Peng Z, Herbst RS, Papadimitrakopoulou V, Minna JD, Peyton M, Roth JA. Combination Treatment with MEK and AKT Inhibitors Is More Effective than Each Drug Alone in Human Non-Small Cell Lung Cancer In Vitro and In Vivo. PLOS ONE 2010, 5: e14124. PMID: 21124782, PMCID: PMC2993951, DOI: 10.1371/journal.pone.0014124.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic Combined Chemotherapy ProtocolsApoptosisBenzimidazolesCarcinoma, Non-Small-Cell LungCell CycleCell Line, TumorCell SurvivalDose-Response Relationship, DrugDrug SynergismFemaleHeterocyclic Compounds, 3-RingHumansLung NeoplasmsMiceMice, Inbred BALB CMice, NudeMitogen-Activated Protein Kinase KinasesProto-Oncogene Proteins c-aktSignal TransductionSurvival AnalysisTumor BurdenXenograft Model Antitumor AssaysConceptsNon-small cell lung cancerCell lung cancerCombination of AZD6244Lung cancer cell linesCombination therapyLung cancerCancer cell linesTumor growthTumor tissueHuman non-small cell lung cancerLung cancer cell growthCell linesHuman lung cancer cell linesSingle drug treatmentSynergistic antitumor activityHuman lung tumorsAnimal survival timeMean animal survival timeCancer cell growthXenograft tumor growthP-AKT expressionLung tumorsDrug treatmentDrug combinationsSurvival time
2008
Lung Cancer
Herbst RS, Heymach JV, Lippman SM. Lung Cancer. New England Journal Of Medicine 2008, 359: 1367-1380. PMID: 18815398, PMCID: PMC10662965, DOI: 10.1056/nejmra0802714.Peer-Reviewed Original Research
2007
Targeted 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 inhibitorsVandetanib (ZD6474): an orally available receptor tyrosine kinase inhibitor that selectively targets pathways critical for tumor growth and angiogenesis
Herbst RS, Heymach JV, O’Reilly M, Onn A, Ryan AJ. Vandetanib (ZD6474): an orally available receptor tyrosine kinase inhibitor that selectively targets pathways critical for tumor growth and angiogenesis. Expert Opinion On Investigational Drugs 2007, 16: 239-249. PMID: 17243944, DOI: 10.1517/13543784.16.2.239.Peer-Reviewed Original ResearchConceptsTumor typesHereditary medullary thyroid cancerReceptor tyrosine kinase inhibitorsPhase III trialsProgression-free survivalDaily oral administrationPhase II evaluationPhase I studiesMedullary thyroid cancerTyrosine kinase inhibitorsSolid tumor typesTumor cell proliferationRefractory NSCLCAdvanced NSCLCIII trialsI studiesII evaluationThyroid cancerOral administrationAvailable agentsClinical developmentPharmacokinetic profileTumor growthVandetanibTumor angiogenesis
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