2022
COAST: An Open-Label, Phase II, Multidrug Platform Study of Durvalumab Alone or in Combination With Oleclumab or Monalizumab in Patients With Unresectable, Stage III Non–Small-Cell Lung Cancer
Herbst RS, Majem M, Barlesi F, Carcereny E, Chu Q, Monnet I, Sanchez-Hernandez A, Dakhil S, Camidge DR, Winzer L, Soo-Hoo Y, Cooper ZA, Kumar R, Bothos J, Aggarwal C, Martinez-Marti A. COAST: An Open-Label, Phase II, Multidrug Platform Study of Durvalumab Alone or in Combination With Oleclumab or Monalizumab in Patients With Unresectable, Stage III Non–Small-Cell Lung Cancer. Journal Of Clinical Oncology 2022, 40: 3383-3393. PMID: 35452273, DOI: 10.1200/jco.22.00227.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalAntineoplastic AgentsCarcinoma, Non-Small-Cell LungChemoradiotherapyDrug CombinationsHumansLung NeoplasmsNeoplasm StagingConceptsProgression-free survivalCell lung cancerUnresectable stage IIIConcurrent chemoradiotherapyLung cancerEastern Cooperative Oncology Group performance status 0/1Stage IIITreatment-emergent adverse eventsPerformance status 0/1Objective response ratePrimary end pointPhase II studyPhase III trialsStandard of careSignificant safety signalsPFS ratesConsolidation therapyOpen labelII studyIII trialsOverall survivalAdverse eventsDurvalumabSafety signalsMonalizumabDevelopment of an immunohistochemical assay for Siglec-15
Shafi S, Aung TN, Robbins C, Zugazagoitia J, Vathiotis I, Gavrielatou N, Yaghoobi V, Fernandez A, Niu S, Liu LN, Cusumano ZT, Leelatian N, Cole K, Wang H, Homer R, Herbst RS, Langermann S, Rimm DL. Development of an immunohistochemical assay for Siglec-15. Laboratory Investigation 2022, 102: 771-778. PMID: 35459795, PMCID: PMC9253057, DOI: 10.1038/s41374-022-00785-9.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalB7-H1 AntigenCarcinoma, Non-Small-Cell LungHumansImmunohistochemistryLung NeoplasmsSialic Acid Binding Immunoglobulin-like LectinsConceptsSiglec-15IHC assaysPD-L1PD-1/PD-L1 inhibitionPD-L1 blockadePD-L1 inhibitionHigh expressionFuture clinical trialsImmunoglobulin-type lectinsSiglec-15 expressionCompanion diagnostic assayPromising new targetTumor histologyImmunotherapeutic targetLung cancerImmune cellsClinical trialsNovel recombinant antibodiesCancer histologyImmunohistochemical assaysMyeloid cellsTumor typesScoring systemNew targetsHigh concordance
2021
Phase II study of durvalumab plus tremelimumab as therapy for patients with previously treated anti-PD-1/PD-L1 resistant stage IV squamous cell lung cancer (Lung-MAP substudy S1400F, NCT03373760)
Leighl NB, Redman MW, Rizvi N, Hirsch FR, Mack PC, Schwartz LH, Wade JL, Irvin WJ, Reddy SC, Crawford J, Bradley JD, Stinchcombe TE, Ramalingam SS, Miao J, Minichiello K, Herbst RS, Papadimitrakopoulou VA, Kelly K, Gandara DR. Phase II study of durvalumab plus tremelimumab as therapy for patients with previously treated anti-PD-1/PD-L1 resistant stage IV squamous cell lung cancer (Lung-MAP substudy S1400F, NCT03373760). Journal For ImmunoTherapy Of Cancer 2021, 9: e002973. PMID: 34429332, PMCID: PMC8386207, DOI: 10.1136/jitc-2021-002973.Peer-Reviewed Original ResearchConceptsDisease progressionAnti-programmed death ligand 1 therapyStage IV squamous cell lung cancerPrior anti-PD-1 therapyResponse rateAnti-PD-1 therapyDeath ligand 1 therapyMedian progression-free survivalSquamous cell lung cancerObjective response ratePhase II studyProgression-free survivalCell lung cancerSquamous lung carcinomaDurvalumab 1500Eligible patientsImmunotherapy combinationsPrimary endpointAdverse eventsII studyOverall survivalPartial responseTRIAL REGISTRATIONLung cancerLung carcinomaSelecting the optimal immunotherapy regimen in driver-negative metastatic NSCLC
Grant MJ, Herbst RS, Goldberg SB. Selecting the optimal immunotherapy regimen in driver-negative metastatic NSCLC. Nature Reviews Clinical Oncology 2021, 18: 625-644. PMID: 34168333, DOI: 10.1038/s41571-021-00520-1.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalCarcinoma, Non-Small-Cell LungHumansImmunotherapyLung NeoplasmsMolecular Targeted TherapyProgrammed Cell Death 1 ReceptorConceptsSubset of patientsTreatment landscapeRegimen selectionTumor cell PD-L1 expressionChemotherapy-immunotherapy combinationsImmune checkpoint inhibitorsTreatment-naive patientsFirst-line therapyPD-L1 expressionCurrent treatment landscapeCell lung cancerAbsence of headCurrent treatment paradigmsPivotal clinical trialsLong-term efficacyNovel therapeutic strategiesImmunotherapy regimenMetastatic NSCLCImmunotherapeutic strategiesClinicopathological factorsPD-1PD-L1Durable efficacyHistological subtypesLung cancer
2020
SWOG S1400A (NCT02154490): A Phase II Study of Durvalumab for Patients With Previously Treated Stage IV or Recurrent Squamous Cell Lung Cancer (Lung-MAP Sub-study)
Borghaei H, Redman MW, Kelly K, Waqar SN, Robert F, Kiefer GJ, Stella PJ, Minichiello K, Gandara DR, Herbst RS, Papadimitrakopoulou VA. SWOG S1400A (NCT02154490): A Phase II Study of Durvalumab for Patients With Previously Treated Stage IV or Recurrent Squamous Cell Lung Cancer (Lung-MAP Sub-study). Clinical Lung Cancer 2020, 22: 178-186. PMID: 33358401, PMCID: PMC8686189, DOI: 10.1016/j.cllc.2020.10.015.Peer-Reviewed Original ResearchConceptsDisease control rateMedian overall survivalProgression-free survivalCell lung cancerAdverse eventsOverall survivalControl rateLung cancerRecurrent squamous cell lung cancerPhase II/III trialsDrug-related adverse eventsMedian progression-free survivalPrior platinum-based chemotherapyTreatment-related adverse eventsSquamous cell lung cancerPD-L1 dataPhase II studyPhase II trialPD-L1 antibodiesPlatinum-based chemotherapySingle-agent activityEvaluable patientsII trialPrimary endpointII studyA Phase II Study of Telisotuzumab Vedotin in Patients With c–MET-positive Stage IV or Recurrent Squamous Cell Lung Cancer (LUNG-MAP Sub-study S1400K, NCT03574753)
Waqar SN, Redman MW, Arnold SM, Hirsch FR, Mack PC, Schwartz LH, Gandara DR, Stinchcombe TE, Leighl NB, Ramalingam SS, Tanna SH, Raddin RS, Minichiello K, Bradley JD, Kelly K, Herbst RS, Papadimitrakopoulou VA. A Phase II Study of Telisotuzumab Vedotin in Patients With c–MET-positive Stage IV or Recurrent Squamous Cell Lung Cancer (LUNG-MAP Sub-study S1400K, NCT03574753). Clinical Lung Cancer 2020, 22: 170-177. PMID: 33221175, PMCID: PMC8044254, DOI: 10.1016/j.cllc.2020.09.013.Peer-Reviewed Original ResearchMeSH KeywordsAgedAged, 80 and overAntibodies, MonoclonalAntineoplastic AgentsCarcinoma, Non-Small-Cell LungCarcinoma, Squamous CellCohort StudiesFemaleHumansLung NeoplasmsMaleMiddle AgedNeoplasm Recurrence, LocalNeoplasm StagingPneumoniaProgression-Free SurvivalProto-Oncogene Proteins c-metSurvival RateTreatment OutcomeConceptsSquamous cell carcinomaProgression-free survivalTelisotuzumab vedotinCohort 1Recurrent squamous cell lung cancerSquamous cell lung cancerGrade 5 eventsMET-positive tumorsSolid Tumors v1.1Disease control ratePhase II studyResponse Evaluation CriteriaCell lung cancerDuration of responseLack of efficacyEvaluable patientsStable diseasePrimary endpointSecondary endpointsUnacceptable toxicityII studyOverall survivalCell carcinomaControl rateLung cancer
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-1Ramucirumab Plus Pembrolizumab in Patients with Previously Treated Advanced or Metastatic Biliary Tract Cancer: Nonrandomized, Open‐Label, Phase I Trial (JVDF)
Arkenau H, Martin‐Liberal J, Calvo E, Penel N, Krebs MG, Herbst RS, Walgren RA, Widau RC, Mi G, Jin J, Ferry D, Chau I. Ramucirumab Plus Pembrolizumab in Patients with Previously Treated Advanced or Metastatic Biliary Tract Cancer: Nonrandomized, Open‐Label, Phase I Trial (JVDF). The Oncologist 2018, 23: 1407-e136. PMID: 29853658, PMCID: PMC6292555, DOI: 10.1634/theoncologist.2018-0044.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBile Duct NeoplasmsFemaleHumansMaleMiddle AgedConceptsMetastatic biliary tract cancerTreatment-related adverse eventsBiliary tract cancerObjective response rateProgression-free survivalOverall survivalTract cancerCommon grade 3 treatment-related adverse eventsGrade 3 treatment-related adverse eventsGrade 4 treatment-related adverse eventsDay 1Response rateAdvanced biliary tract cancerMedian progression-free survivalBiomarker-unselected patientsEfficacy of ramucirumabInfrequent grade 3Limited clinical activityPD-1 antagonistsTreatment-related deathsUnexpected safety findingsVEGFR-2 antagonistGrowth factor receptor 2Phase I trialExtrahepatic bile ductDefining and Understanding Adaptive Resistance in Cancer Immunotherapy
Kim TK, Herbst RS, Chen L. Defining and Understanding Adaptive Resistance in Cancer Immunotherapy. Trends In Immunology 2018, 39: 624-631. PMID: 29802087, PMCID: PMC6066429, DOI: 10.1016/j.it.2018.05.001.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityAntibodies, MonoclonalB7-H1 AntigenDrug ResistanceImmunotherapyNeoplasmsProgrammed Cell Death 1 ReceptorTumor EscapeTumor MicroenvironmentConceptsAnti-PD therapyLong-term survival benefitAvailable treatment regimensFraction of respondersSurvival benefitTumor immunityTumor-immune interactionsAdvanced cancerTreatment regimensCancer immunotherapyTumor regressionTherapyAccurate tissueSuch treatmentAdaptive resistancePatientsMolecular mechanismsTrue resistanceImmunotherapyRegimensRight targetCancerRespondersImmunityAppropriate interpretation
2017
Immunotherapy in Lung Cancer
Du L, Herbst RS, Morgensztern D. Immunotherapy in Lung Cancer. Hematology/Oncology Clinics Of North America 2017, 31: 131-141. PMID: 27912829, DOI: 10.1016/j.hoc.2016.08.004.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerCell lung cancerLung cancerAdvanced stage non-small cell lung cancerPD-1/PD-L1 axisFirst-line platinum-based doubletStage non-small cell lung cancerApproval of nivolumabPlatinum-based doubletsSecond-line docetaxelGood performance statusImmune checkpoint inhibitorsPD-L1 axisMinority of patientsRandomized clinical trialsTreatment of patientsNew therapeutic approachesClass of drugsCheckpoint inhibitorsOverall survivalPerformance statusClinical trialsProlonged benefitTherapeutic approachesPatients
2016
Nivolumab and Pembrolizumab for Non–Small Cell Lung Cancer
Morgensztern D, Herbst RS. Nivolumab and Pembrolizumab for Non–Small Cell Lung Cancer. Clinical Cancer Research 2016, 22: 3713-3717. PMID: 27252413, DOI: 10.1158/1078-0432.ccr-15-2998.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Non-Small-Cell LungClinical Trials, Phase I as TopicHumansLung NeoplasmsNivolumabPrognosisProgrammed Cell Death 1 ReceptorRandomized Controlled Trials as TopicTreatment OutcomeConceptsCheckpoint inhibitorsClinical trialsAdvanced stage non-small lung cancerDeath-1 checkpoint inhibitorsLarge randomized clinical trialsNon-small lung cancerSecond-line docetaxelSurvivors 3 yearsBest supportive careSubset of patientsRandomized clinical trialsOverall survivalSupportive careCombination therapyLung cancerModest benefitPatientsPhase IImmunotherapyReliable predictorTherapyInhibitorsTrialsTreatmentNivolumabPredictive Biomarkers for PD-1 Axis Therapies: The Hidden Treasure or a Call for Research
Schalper KA, Kaftan E, Herbst RS. Predictive Biomarkers for PD-1 Axis Therapies: The Hidden Treasure or a Call for Research. Clinical Cancer Research 2016, 22: 2102-2104. PMID: 26957559, PMCID: PMC4940186, DOI: 10.1158/1078-0432.ccr-16-0169.Peer-Reviewed Original ResearchQuantitative Assessment of the Heterogeneity of PD-L1 Expression in Non–Small-Cell Lung Cancer
McLaughlin J, Han G, Schalper KA, Carvajal-Hausdorf D, Pelakanou V, Rehman J, Velcheti V, Herbst R, LoRusso P, Rimm DL. Quantitative Assessment of the Heterogeneity of PD-L1 Expression in Non–Small-Cell Lung Cancer. JAMA Oncology 2016, 2: 1-9. PMID: 26562159, PMCID: PMC4941982, DOI: 10.1001/jamaoncol.2015.3638.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntibodies, MonoclonalAntibody SpecificityB7-H1 AntigenBiomarkers, TumorCarcinoma, Non-Small-Cell LungFemaleFluorescent Antibody TechniqueHumansImmunohistochemistryLung NeoplasmsMaleObserver VariationPredictive Value of TestsReproducibility of ResultsRetrospective StudiesTissue Array AnalysisConceptsTumor-infiltrating lymphocytesPD-L1 expressionPD-L1 antibodiesPD-L1 protein expressionCell lung cancerPD-L1Whole tissue sectionsQuantitative immunofluorescenceLung cancerChromogenic immunohistochemistryPoor concordanceDifferent PD-L1 antibodiesHigh tumor-infiltrating lymphocytesTumor PD-L1 expressionPD-L1 protein levelsCell lung cancer biopsiesMonoclonal antibodiesCurrent consensus guidelinesProtein expressionDurable clinical responsesMain outcome measuresEarly phase trialsLung cancer biopsiesRabbit monoclonal antibodyCorresponding tissue microarrays
2014
Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients
Herbst RS, Soria JC, Kowanetz M, Fine GD, Hamid O, Gordon MS, Sosman JA, McDermott DF, Powderly JD, Gettinger SN, Kohrt HE, Horn L, Lawrence DP, Rost S, Leabman M, Xiao Y, Mokatrin A, Koeppen H, Hegde PS, Mellman I, Chen DS, Hodi FS. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature 2014, 515: 563-567. PMID: 25428504, PMCID: PMC4836193, DOI: 10.1038/nature14011.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedB7-H1 AntigenBiomarkersChemokine CX3CL1Clinical ProtocolsCTLA-4 AntigenDisease-Free SurvivalFemaleGene Expression Regulation, NeoplasticHumansImmunotherapyLymphocytes, Tumor-InfiltratingMaleMiddle AgedNeoplasmsTreatment OutcomeYoung AdultThe PD-1 pathway as a therapeutic target to overcome immune escape mechanisms in cancer
Henick BS, Herbst RS, Goldberg SB. The PD-1 pathway as a therapeutic target to overcome immune escape mechanisms in cancer. Expert Opinion On Therapeutic Targets 2014, 18: 1407-1420. PMID: 25331677, DOI: 10.1517/14728222.2014.955794.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, MonoclonalAntineoplastic AgentsClinical Trials as TopicHumansImmunotherapyNeoplasmsProgrammed Cell Death 1 ReceptorTumor EscapeConceptsPD-1 pathwayEarly clinical trialsClinical trialsTumor typesDeath-1 pathway inhibitorsPD-1 pathway inhibitionImmune escape mechanismsOngoing clinical trialsEarly-stage cancerTreatment of cancerCure rateLikely respondersCancer immunotherapyPreclinical dataAntineoplastic effectsTherapeutic targetPathway inhibitionPathway inhibitorCancer typesBiological rationaleCancer treatmentMonoclonal antibodiesEscape mechanismsUpcoming trialsTrials“Companion Diagnostics”: Has Their Time Come and Gone?
Hirsch FR, Bunn PA, Herbst RS. “Companion Diagnostics”: Has Their Time Come and Gone? Clinical Cancer Research 2014, 20: 4422-4424. PMID: 25059519, PMCID: PMC4155019, DOI: 10.1158/1078-0432.ccr-14-0932.Peer-Reviewed Original Research
2012
Design of a Phase III Clinical Trial with Prospective Biomarker Validation: SWOG S0819
Redman MW, Crowley JJ, Herbst RS, Hirsch FR, Gandara DR. Design of a Phase III Clinical Trial with Prospective Biomarker Validation: SWOG S0819. Clinical Cancer Research 2012, 18: 4004-4012. PMID: 22592956, PMCID: PMC3409929, DOI: 10.1158/1078-0432.ccr-12-0167.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic AgentsBiomarkers, TumorCarcinoma, Non-Small-Cell LungCetuximabClinical Trials, Phase III as TopicDisease-Free SurvivalErbB ReceptorsHumansIn Situ Hybridization, FluorescenceLung NeoplasmsPrognosisProspective StudiesResearch DesignTreatment OutcomeConceptsNon-small cell lung cancerEpidermal growth factor receptorPredictive biomarkersStudy populationAdvanced non-small cell lung cancerEGFR FISH-positive patientsPhase III clinical trialsRole of cetuximabOverall study populationPhase III trialsCell lung cancerEntire study populationFISH-positive patientsInterim monitoring planGrowth factor receptorCoprimary endpointsIII trialsCetuximab efficacyLung cancerClinical trialsPositive groupCetuximabEGFR FISHFactor receptorMolecular targets
2011
Phase II Study of Cetuximab in Combination With Chemoradiation in Patients With Stage IIIA/B Non–Small-Cell Lung Cancer: RTOG 0324
Blumenschein GR, Paulus R, Curran WJ, Robert F, Fossella F, Werner-Wasik M, Herbst RS, Doescher PO, Choy H, Komaki R. Phase II Study of Cetuximab in Combination With Chemoradiation in Patients With Stage IIIA/B Non–Small-Cell Lung Cancer: RTOG 0324. Journal Of Clinical Oncology 2011, 29: 2312-2318. PMID: 21555682, PMCID: PMC3107747, DOI: 10.1200/jco.2010.31.7875.Peer-Reviewed Original ResearchConceptsUnresectable stage III NSCLCEpidermal growth factor receptorStage III NSCLCCombination of cetuximabCell lung cancerOverall survivalLung cancerGrade 4 hematologic toxicityRadiation Therapy Oncology GroupAdequate organ functionCycles of paclitaxelGrade 3 esophagitisGrade 5 eventsZubrod performance statusPhase II studyPrimary end pointCompletion of therapyPhase II trialDoses of paclitaxelPoor clinical outcomeGrowth factor receptorWeekly carboplatinHematologic toxicityII trialAdverse eventsEfficacy of bevacizumab plus erlotinib versus erlotinib alone in advanced non-small-cell lung cancer after failure of standard first-line chemotherapy (BeTa): a double-blind, placebo-controlled, phase 3 trial
Herbst RS, Ansari R, Bustin F, Flynn P, Hart L, Otterson GA, Vlahovic G, Soh CH, O'Connor P, Hainsworth J. Efficacy of bevacizumab plus erlotinib versus erlotinib alone in advanced non-small-cell lung cancer after failure of standard first-line chemotherapy (BeTa): a double-blind, placebo-controlled, phase 3 trial. The Lancet 2011, 377: 1846-1854. PMID: 21621716, PMCID: PMC4134127, DOI: 10.1016/s0140-6736(11)60545-x.Peer-Reviewed Original ResearchMeSH KeywordsAgedAngiogenesis InhibitorsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBevacizumabCarcinoma, Non-Small-Cell LungDisease-Free SurvivalDouble-Blind MethodErlotinib HydrochlorideFemaleHumansLung NeoplasmsMaleMiddle AgedProportional Hazards ModelsProtein Kinase InhibitorsQuinazolinesSurvival RateVascular Endothelial Growth Factor AConceptsPhase 3 trialBevacizumab groupCell lung cancerAdverse eventsOverall survivalRefractory NSCLCPrimary endpointLung cancerControl groupComputer-generated randomisation sequenceGrade 5 adverse eventsStandard first-line chemotherapyCalculation of incidenceEfficacy of bevacizumabArterial thromboembolic eventsFirst-line chemotherapyMedian overall survivalObjective response rateSerious adverse eventsAddition of bevacizumabFirst-line treatmentPhase 1/2 trialProgression-free survivalToxic effect profilesActivity of erlotinibUpregulated 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