Featured Publications
Future Directions in the Management of Non-Small Cell Lung Cancer Harboring Driver Mutations.
Herbst RS. Future Directions in the Management of Non-Small Cell Lung Cancer Harboring Driver Mutations. Oncology 2022, 36: 562-563. PMID: 36107783, DOI: 10.46883/2022.25920974.Peer-Reviewed Original ResearchAdenocarcinoma of LungAnaplastic Lymphoma KinaseCarcinoma, Non-Small-Cell LungHumansLung NeoplasmsMutation
2022
Quantitative tissue analysis and role of myeloid cells in non-small cell lung cancer
Henick BS, Villarroel-Espindola F, Datar I, Sanmamed MF, Yu J, Desai S, Li A, Aguirre-Ducler A, Syrigos K, Rimm DL, Chen L, Herbst RS, Schalper KA. Quantitative tissue analysis and role of myeloid cells in non-small cell lung cancer. Journal For ImmunoTherapy Of Cancer 2022, 10: e005025. PMID: 35793873, PMCID: PMC9260844, DOI: 10.1136/jitc-2022-005025.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinoma of LungCarcinoma, Non-Small-Cell LungCarcinoma, Squamous CellHLA-DR AntigensHumansLung NeoplasmsMyeloid CellsRetrospective StudiesConceptsNon-small cell lung cancerSquamous cell carcinomaHuman non-small cell lung cancerMyeloid cell subsetsCell lung cancerHLA-DRLung adenocarcinomaMyeloid cellsCell subsetsLung cancerLung tissueQuantitative immunofluorescenceNon-tumor lung tissuesIndependent NSCLC cohortsLevels of CD68Multiplexed quantitative immunofluorescenceProinflammatory myeloid cellsHLA-DR expressionM1-like macrophagesImmature myeloid cell populationMyeloid cell populationsKRAS mutant tumorsNormal lung tissuesTumor epithelial cellsNon-tumor lungRASGRF1 Fusions Activate Oncogenic RAS Signaling and Confer Sensitivity to MEK Inhibition.
Hunihan L, Zhao D, Lazowski H, Li M, Qian Y, Abriola L, Surovtseva YV, Muthusamy V, Tanoue LT, Rothberg BE, Schalper KA, Herbst RS, Wilson FH. RASGRF1 Fusions Activate Oncogenic RAS Signaling and Confer Sensitivity to MEK Inhibition. Clinical Cancer Research 2022, 28: 3091-3103. PMID: 35247929, PMCID: PMC9288503, DOI: 10.1158/1078-0432.ccr-21-4291.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinoma of LungCarcinogenesisHumansLung NeoplasmsMitogen-Activated Protein Kinase KinasesRas-GRF1ConceptsLung adenocarcinomaSmoking historyPack-year smoking historyMinimal smoking historySubset of patientsPancreatic ductal adenocarcinoma cell linesPotential treatment strategyTight junction protein occludinJunction protein occludinWhole-exome sequencingAdenocarcinoma cell lineAdvanced malignanciesCancer Genome AtlasRaf-MEKAdvanced tumorsMultiple malignanciesTreatment strategiesKRAS mutationsTherapeutic strategiesTherapeutic targetOncogenic RAS SignalingRelated commentaryOncogenic driversMEK inhibitionOncogenic alterations
2021
Targeted therapies for resectable lung adenocarcinoma: ADAURA opens for thoracic oncologic surgeons
Jones DR, Wu YL, Tsuboi M, Herbst RS. Targeted therapies for resectable lung adenocarcinoma: ADAURA opens for thoracic oncologic surgeons. Journal Of Thoracic And Cardiovascular Surgery 2021, 162: 288-292. PMID: 33691940, PMCID: PMC8519337, DOI: 10.1016/j.jtcvs.2021.02.008.Peer-Reviewed Original Research
2019
The Combination of MEK Inhibitor With Immunomodulatory Antibodies Targeting Programmed Death 1 and Programmed Death Ligand 1 Results in Prolonged Survival in Kras/p53-Driven Lung Cancer
Lee JW, Zhang Y, Eoh KJ, Sharma R, Sanmamed MF, Wu J, Choi J, Park HS, Iwasaki A, Kaftan E, Chen L, Papadimitrakopoulou V, Herbst RS, Koo JS. The Combination of MEK Inhibitor With Immunomodulatory Antibodies Targeting Programmed Death 1 and Programmed Death Ligand 1 Results in Prolonged Survival in Kras/p53-Driven Lung Cancer. Journal Of Thoracic Oncology 2019, 14: 1046-1060. PMID: 30771521, PMCID: PMC6542636, DOI: 10.1016/j.jtho.2019.02.004.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinoma of LungAnimalsAntineoplastic Agents, ImmunologicalAntineoplastic Combined Chemotherapy ProtocolsB7-H1 AntigenDrug SynergismFemaleLung NeoplasmsMAP Kinase Kinase KinasesMiceMice, KnockoutMice, TransgenicMyeloid-Derived Suppressor CellsProgrammed Cell Death 1 ReceptorProtein Kinase InhibitorsProto-Oncogene Proteins p21(ras)PyridonesPyrimidinonesSurvival AnalysisTumor Suppressor Protein p53ConceptsImmune cell populationsLung tumorsMEK inhibitorsDeath-1Survival outcomesLung cancerL1 mAbsTumor-infiltrating immune cell populationsTumor-infiltrating immune cellsCell death ligand 1Flow cytometryLung cancer mouse modelAdenoviral Cre recombinaseAutochthonous lung tumorsImmunomodulatory monoclonal antibodiesTumor-infiltrating CD8PD-L1 expressionSingle-agent therapyTumor-bearing lungsDeath ligand 1Tumor-free miceLung cancer modelCombinatorial antitumor effectCancer mouse modelCell populations
2017
Extracellular Matrix Receptor Expression in Subtypes of Lung Adenocarcinoma Potentiates Outgrowth of Micrometastases
Stevens LE, Cheung WKC, Adua SJ, Arnal-Estapé A, Zhao M, Liu Z, Brewer K, Herbst RS, Nguyen DX. Extracellular Matrix Receptor Expression in Subtypes of Lung Adenocarcinoma Potentiates Outgrowth of Micrometastases. Cancer Research 2017, 77: 1905-1917. PMID: 28196904, PMCID: PMC5468792, DOI: 10.1158/0008-5472.can-16-1978.Peer-Reviewed Original ResearchConceptsBrain metastatic nicheRisk of relapseDistant metastasisPoor prognosisLUAD subtypesLung tumorsLung adenocarcinomaLUAD cellsMetastatic outgrowthMetastatic nicheCancer ResCancer cellsECM-mediated signalingExtracellular matrix moleculesCell survivalMolecular signaturesDifferential expressionHMMRMatrix moleculesImportant mechanismCellsRelapseAdenocarcinomaPrognosisMetastasisWhole-exome sequencing and immune profiling of early-stage lung adenocarcinoma with fully annotated clinical follow-up
Kadara H, Choi M, Zhang J, Parra ER, Rodriguez-Canales J, Gaffney SG, Zhao Z, Behrens C, Fujimoto J, Chow C, Yoo Y, Kalhor N, Moran C, Rimm D, Swisher S, Gibbons DL, Heymach J, Kaftan E, Townsend JP, Lynch TJ, Schlessinger J, Lee J, Lifton RP, Wistuba II, Herbst RS. Whole-exome sequencing and immune profiling of early-stage lung adenocarcinoma with fully annotated clinical follow-up. Annals Of Oncology 2017, 28: 75-82. PMID: 27687306, PMCID: PMC5982809, DOI: 10.1093/annonc/mdw436.Peer-Reviewed Original ResearchConceptsRecurrence-free survivalPoor recurrence-free survivalWhole-exome sequencingEarly-stage lung adenocarcinomaMutant lung adenocarcinomaLung adenocarcinomaImmune markersClinical outcomesExact testNatural killer cell infiltrationProportional hazards regression modelsGranzyme B levelsImmune marker analysisImmune profiling analysisPD-L1 expressionImmune-based therapiesTumoral PD-L1Hazards regression modelsKRAS mutant tumorsNormal lung tissuesMajority of deathsFisher's exact testHigh mutation burdenAnalysis of immunophenotypeRelevant molecular markers
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 moleculesA Novel Small-Molecule Inhibitor Targeting CREB-CBP Complex Possesses Anti-Cancer Effects along with Cell Cycle Regulation, Autophagy Suppression and Endoplasmic Reticulum Stress
Lee JW, Park HS, Park SA, Ryu SH, Meng W, Jürgensmeier JM, Kurie JM, Hong WK, Boyer JL, Herbst RS, Koo JS. A Novel Small-Molecule Inhibitor Targeting CREB-CBP Complex Possesses Anti-Cancer Effects along with Cell Cycle Regulation, Autophagy Suppression and Endoplasmic Reticulum Stress. PLOS ONE 2015, 10: e0122628. PMID: 25897662, PMCID: PMC4405579, DOI: 10.1371/journal.pone.0122628.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdenocarcinoma of LungAnilidesAntineoplastic AgentsApoptosis Regulatory ProteinsAutophagyAutophagy-Related Protein 7Bcl-2-Like Protein 11Cell Cycle CheckpointsCell Line, TumorCyclic AMP Response Element-Binding ProteinDrug Screening Assays, AntitumorEndoplasmic Reticulum StressHumansInhibitory Concentration 50Kaplan-Meier EstimateLung NeoplasmsMembrane ProteinsMolecular Docking SimulationOrganophosphatesPeptide FragmentsProportional Hazards ModelsProtein BindingProto-Oncogene ProteinsSialoglycoproteinsUbiquitin-Activating EnzymesConceptsLung cancerHuman lung cancer cell linesEndoplasmic reticulum (ER) stress markersLung cancer cell linesNovel therapeutic strategiesPotential therapeutic targetAnti-cancer effectsNovel small molecule inhibitorPotential therapeutic agentCyclic AMP response element binding proteinAccumulation of p62Response element-binding proteinEndoplasmic reticulum stressCancer cell linesCancer deathCommon subtypeCell cycle arrestLung adenocarcinomaNew therapiesTherapeutic strategiesSmall molecule inhibitorsTherapeutic targetElement-binding proteinStress markersTherapeutic agents
2014
Angiogenesis inhibition and lung-cancer therapy
Onn A, Bar J, Herbst RS. Angiogenesis inhibition and lung-cancer therapy. The Lancet Oncology 2014, 15: 124-125. PMID: 24480554, DOI: 10.1016/s1470-2045(14)70010-5.Peer-Reviewed Original Research
2013
CXCR2 Expression in Tumor Cells Is a Poor Prognostic Factor and Promotes Invasion and Metastasis in Lung Adenocarcinoma
Saintigny P, Massarelli E, Lin S, Ahn YH, Chen Y, Goswami S, Erez B, O'Reilly MS, Liu D, Lee JJ, Zhang L, Ping Y, Behrens C, Soto L, Heymach JV, Kim ES, Herbst RS, Lippman SM, Wistuba II, Hong WK, Kurie JM, Koo JS. CXCR2 Expression in Tumor Cells Is a Poor Prognostic Factor and Promotes Invasion and Metastasis in Lung Adenocarcinoma. Cancer Research 2013, 73: 571-582. PMID: 23204236, PMCID: PMC3548940, DOI: 10.1158/0008-5472.can-12-0263.Peer-Reviewed Original ResearchConceptsGene expression profilesNon-small cell lung cancerKnockdown clonesNSCLC cell linesHuman NSCLC cell linesExpression profilesCell linesStable knockdown clonesLung adenocarcinomaLung adenocarcinoma cell linesTumor cellsRAS pathway activationCXCR2 expressionPoor prognosisLung cancer cellsOrthotopic syngeneic mouse modelAdenocarcinoma cell linePromotes InvasionExpression of CXCL5Role of CXCR2Poor prognostic factorCell lung cancerPromoter methylationSyngeneic mouse modelProtein expression
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