2022
RASGRF1 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 ResearchConceptsLung 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
2015
E2F8 as a Novel Therapeutic Target for Lung Cancer
Park SA, Platt J, Lee JW, López-Giráldez F, Herbst RS, Koo JS. E2F8 as a Novel Therapeutic Target for Lung Cancer. Journal Of The National Cancer Institute 2015, 107: djv151. PMID: 26089541, PMCID: PMC4651101, DOI: 10.1093/jnci/djv151.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsCCAAT-Enhancer-Binding ProteinsCell Line, TumorCell ProliferationCell SurvivalChromatin ImmunoprecipitationFluorescent Antibody TechniqueGene Expression Regulation, NeoplasticHumansImmunoblottingKaplan-Meier EstimateLung NeoplasmsMiceMolecular Targeted TherapyNeoplastic Stem CellsPromoter Regions, GeneticRepressor ProteinsTissue Array AnalysisUbiquitin-Protein LigasesUp-RegulationXenograft Model Antitumor AssaysConceptsTarget genesCell cycle regulationNovel therapeutic targetPromoter activity assaysCell proliferationCancer cellsExpression of UHRF1Transcription activatorAntisense morpholinoChromatin immunoprecipitationCycle regulationTherapeutic targetEmbryonic developmentE2F membersHuman lung cancer cellsMicroarray analysisInvasion analysisLung cancer cellsDirect bindingTumor growthE2F8Activity assaysPublic databasesColony formationUHRF1Lung Cancer in the Era of Precision Medicine
Politi K, Herbst RS. Lung Cancer in the Era of Precision Medicine. Clinical Cancer Research 2015, 21: 2213-2220. PMID: 25979927, PMCID: PMC4505624, DOI: 10.1158/1078-0432.ccr-14-2748.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsLung cancerClinical trialsBiomarker-driven clinical trialsLung cancer clinicEfficacy of immunotherapyLung cancer patientsLung cancer subtypesNovel therapeutic targetPrecision medicineFirst-generation drugsMetastatic diseaseCancer patientsEGFR mutationsCancer clinicActionable mutationsTherapeutic targetPatientsMolecular testingCancer subtypesImmune systemNew treatmentsMolecular subgroupsDrug resistanceMechanisms of sensitivityCancerA 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
The 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 ResearchConceptsPD-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
2013
An Epithelial–Mesenchymal Transition Gene Signature Predicts Resistance to EGFR and PI3K Inhibitors and Identifies Axl as a Therapeutic Target for Overcoming EGFR Inhibitor Resistance
Byers LA, Diao L, Wang J, Saintigny P, Girard L, Peyton M, Shen L, Fan Y, Giri U, Tumula PK, Nilsson MB, Gudikote J, Tran H, Cardnell RJ, Bearss DJ, Warner SL, Foulks JM, Kanner SB, Gandhi V, Krett N, Rosen ST, Kim ES, Herbst RS, Blumenschein GR, Lee JJ, Lippman SM, Ang KK, Mills GB, Hong WK, Weinstein JN, Wistuba II, Coombes KR, Minna JD, Heymach JV. An Epithelial–Mesenchymal Transition Gene Signature Predicts Resistance to EGFR and PI3K Inhibitors and Identifies Axl as a Therapeutic Target for Overcoming EGFR Inhibitor Resistance. Clinical Cancer Research 2013, 19: 279-290. PMID: 23091115, PMCID: PMC3567921, DOI: 10.1158/1078-0432.ccr-12-1558.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAxl Receptor Tyrosine KinaseCarcinoma, Non-Small-Cell LungCell Line, TumorCluster AnalysisDrug Resistance, NeoplasmEpithelial-Mesenchymal TransitionErbB ReceptorsGene Expression ProfilingHumansLung NeoplasmsMiceNeoplasm MetastasisPhosphoinositide-3 Kinase InhibitorsProtein Kinase InhibitorsProteomeProteomicsProto-Oncogene ProteinsReceptor Protein-Tyrosine KinasesRecurrenceReproducibility of ResultsConceptsEpithelial-mesenchymal transitionPotential therapeutic targetEGFR inhibitor resistanceTherapeutic targetEMT signatureInhibitor resistanceMesenchymal transition gene signatureMesenchymal cellsCell linesBiomarker-Integrated ApproachesPI3K/Akt pathway inhibitorNon-small cell lung carcinoma cell lineEGFR mutation statusReceptor tyrosine kinase AXLNSCLC cell linesPI3K/Akt inhibitorCell lung carcinoma cell lineGene expression profilesTyrosine kinase AXLLung carcinoma cell linePI3K inhibitorsDrug response analysisAkt pathway inhibitorCarcinoma cell linesErlotinib resistance
2002
Angiogenesis inhibitors in clinical development for lung cancer
Herbst RS, Hidalgo M, Pierson AS, Holden SN, Bergen M, Eckhardt SG. Angiogenesis inhibitors in clinical development for lung cancer. Seminars In Oncology 2002, 29: 66-77. PMID: 11894016, DOI: 10.1053/sonc.2002.31527.Peer-Reviewed Original ResearchMeSH KeywordsAngiogenesis InhibitorsAntineoplastic Combined Chemotherapy ProtocolsClinical Trials as TopicDisease ProgressionEndothelial Growth FactorsEndpoint DeterminationEnzyme InhibitorsHumansLung NeoplasmsLymphokinesMatrix Metalloproteinase InhibitorsMatrix MetalloproteinasesNeovascularization, PathologicTreatment OutcomeVascular Endothelial Growth Factor AVascular Endothelial Growth FactorsConceptsAngiogenesis inhibitorsLung cancerClinical trialsClinical developmentPhase II trialLong-term administrationPlatinum-based therapyEarly clinical trialsReceptor-targeted agentsPrimary endpointAdvanced diseaseII trialMetastatic diseaseAdjunctive therapyProcess of angiogenesisCancer patientsField of angiogenesisEfficacious dosesClinical evaluationTumor regressionNovel agentsAntiangiogenic agentsTherapeutic targetDependence of tumorsTumor angiogenesis
2000
Expression of vascular endothelial growth factor is necessary but not sufficient for production and growth of brain metastasis.
Yano S, Shinohara H, Herbst RS, Kuniyasu H, Bucana CD, Ellis LM, Davis DW, McConkey DJ, Fidler IJ. Expression of vascular endothelial growth factor is necessary but not sufficient for production and growth of brain metastasis. Cancer Research 2000, 60: 4959-67. PMID: 10987313.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrain NeoplasmsCell DivisionCytokinesDNA, AntisenseEndothelial Growth FactorsHumansLymphokinesMaleMiceMice, NudeNeoplasm TransplantationNeovascularization, PathologicRNA, MessengerTransfectionTumor Cells, CulturedVascular Endothelial Growth Factor AVascular Endothelial Growth FactorsConceptsBrain metastasesCell carcinomaHuman lung squamous carcinoma cellsLung squamous carcinoma cellsLung squamous cell carcinomaExperimental brain metastasesParenchymal brain metastasesSquamous cell carcinomaInternal carotid arteryVascular endothelial growth factorRenal cell carcinomaEndothelial growth factorImportant therapeutic targetInhibition of VEGFSquamous carcinoma cellsLung adenocarcinoma cellsCancer cell linesDifferent human cancer cell linesCarotid arteryNude miceTherapeutic targetKM12SM cellsMetastasisHuman cancer cell linesVEGF expression