2018
The biology and management of non-small cell lung cancer
Herbst RS, Morgensztern D, Boshoff C. The biology and management of non-small cell lung cancer. Nature 2018, 553: 446-454. PMID: 29364287, DOI: 10.1038/nature25183.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerCell lung cancerLung cancerSmall molecule tyrosine kinase inhibitorsMolecule tyrosine kinase inhibitorsBroader patient populationTyrosine kinase inhibitorsUnprecedented survival benefitsMetastatic diseaseMultimodal careSurvival benefitClinical benefitCombination therapyOverall curePatient populationSurvival rateTumor progressionEarly detectionKinase inhibitorsNew drugsDisease biologyCancerImmunotherapyPatientsTherapy
2015
Molecularly Targeted Therapies in Non–Small-Cell Lung Cancer Annual Update 2014
Morgensztern D, Campo MJ, Dahlberg SE, Doebele RC, Garon E, Gerber DE, Goldberg SB, Hammerman PS, Heist RS, Hensing T, Horn L, Ramalingam SS, Rudin CM, Salgia R, Sequist LV, Shaw AT, Simon GR, Somaiah N, Spigel DR, Wrangle J, Johnson D, Herbst RS, Bunn P, Govindan R. Molecularly Targeted Therapies in Non–Small-Cell Lung Cancer Annual Update 2014. Journal Of Thoracic Oncology 2015, 10: s1-s63. PMID: 25535693, PMCID: PMC4346098, DOI: 10.1097/jto.0000000000000405.Peer-Reviewed Original Research
2012
Multitargeted Tyrosine Kinase Inhibitors in Unselected Patients With Advanced Non–Small-Cell Lung Cancer (NSCLC): Impressions From MONET (the Motesanib NSCLC Efficacy and Tolerability Study)
Morgensztern D, Herbst RS. Multitargeted Tyrosine Kinase Inhibitors in Unselected Patients With Advanced Non–Small-Cell Lung Cancer (NSCLC): Impressions From MONET (the Motesanib NSCLC Efficacy and Tolerability Study). Journal Of Clinical Oncology 2012, 30: 2805-2808. PMID: 22753916, DOI: 10.1200/jco.2012.42.7260.Peer-Reviewed Original Research
2008
BATTLE: Biomarker-Based Approaches of Targeted Therapy for Lung Cancer Elimination
Hong W, Herbst R, Mao L, Kim E. BATTLE: Biomarker-Based Approaches of Targeted Therapy for Lung Cancer Elimination. 2008 DOI: 10.21236/ada485729.Peer-Reviewed Original ResearchNonsmall cell lung cancerLung cancerTargeted therapyAdvanced nonsmall cell lung cancerEpidermal growth factor receptor tyrosine kinase inhibitorsGrowth factor receptor tyrosine kinase inhibitorsReceptor tyrosine kinase inhibitorsLung Cancer EliminationTumor response rateCell lung cancerLung cancer patientsCancer-related deathTyrosine kinase inhibitorsCancer patientsCancer eliminationEGFR mutationsTherapeutic approachesResponse rateCancerCancer typesPatientsKinase inhibitorsTherapyInitial successChemotherapyEnzastaurin, an Oral Serine/Threonine Kinase Inhibitor, As Second- or Third-Line Therapy of Non–Small-Cell Lung Cancer
Oh Y, Herbst RS, Burris H, Cleverly A, Musib L, Lahn M, Bepler G. Enzastaurin, an Oral Serine/Threonine Kinase Inhibitor, As Second- or Third-Line Therapy of Non–Small-Cell Lung Cancer. Journal Of Clinical Oncology 2008, 26: 1135-1141. PMID: 18309949, DOI: 10.1200/jco.2007.14.3685.Peer-Reviewed Original ResearchConceptsOral serine/threonine kinase inhibitorCell lung cancerPFS ratesMetastatic NSCLCOverall survivalLung cancerEastern Cooperative Oncology Group performance statusSix-month PFS rateProgression-free survival ratesEpidermal growth factor inhibitorsSerine/threonine kinase inhibitorProtein kinase CKinase inhibitorsPrior systemic regimensMedian overall survivalPrimary end pointThird-line therapyPhase II trialGrowth factor inhibitorsTumor cell apoptosisMedian PFSStable diseaseCommon toxicitiesPrior therapySystemic regimens
2007
Enzastaurin, a Protein Kinase Cβ–Selective Inhibitor, and Its Potential Application as an Anticancer Agent in Lung Cancer
Herbst RS, Oh Y, Wagle A, Lahn M. Enzastaurin, a Protein Kinase Cβ–Selective Inhibitor, and Its Potential Application as an Anticancer Agent in Lung Cancer. Clinical Cancer Research 2007, 13: 4641s-4646s. PMID: 17671157, DOI: 10.1158/1078-0432.ccr-07-0538.Peer-Reviewed Original ResearchConceptsSerine/threonine kinase inhibitorLung cancerOral serine/threonine kinase inhibitorProtein kinase CFavorable safety profileCurrent phase IKinase CTumor cell apoptosisAkt pathwayClinical findingsSafety profilePKC inhibitorTumor-induced angiogenesisPreclinical experienceCell apoptosisEnzastaurinKinase inhibitorsPhase ICancerKRAS Mutation Is an Important Predictor of Resistance to Therapy with Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Non–Small-Cell Lung Cancer
Massarelli E, Varella-Garcia M, Tang X, Xavier AC, Ozburn NC, Liu DD, Bekele BN, Herbst RS, Wistuba II. KRAS Mutation Is an Important Predictor of Resistance to Therapy with Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Non–Small-Cell Lung Cancer. Clinical Cancer Research 2007, 13: 2890-2896. PMID: 17504988, DOI: 10.1158/1078-0432.ccr-06-3043.Peer-Reviewed Original ResearchMeSH KeywordsCarcinoma, Non-Small-Cell LungDisease ProgressionDrug Resistance, NeoplasmErbB ReceptorsErlotinib HydrochlorideFemaleGefitinibGene DosageHumansLung NeoplasmsMaleMiddle AgedMutationPrognosisProtein Kinase InhibitorsProto-Oncogene ProteinsProto-Oncogene Proteins p21(ras)QuinazolinesRas ProteinsTreatment OutcomeConceptsEpidermal growth factor receptor tyrosine kinase inhibitorsGrowth factor receptor tyrosine kinase inhibitorsReceptor tyrosine kinase inhibitorsCell lung cancerKRAS mutationsTyrosine kinase inhibitorsEGFR-TKIEGFR copy numberEGFR mutationsLung cancerFavorable responseKinase inhibitorsShorter median timeArchival tissue specimensEGFR gene mutationsPanel of markersAdvanced NSCLCObjective responseProgressive diseaseSurvival benefitMedian timePoor responseSuch therapyDisease progressionPatients
2006
Therapeutic options to target angiogenesis in human malignancies
Herbst RS. Therapeutic options to target angiogenesis in human malignancies. Expert Opinion On Emerging Drugs 2006, 11: 635-650. PMID: 17064223, DOI: 10.1517/14728214.11.4.635.Peer-Reviewed Original ResearchConceptsTyrosine kinase inhibitorsHuman malignanciesMonoclonal antibodiesGrowth factorKinase inhibitorsAnti-VEGF inhibitorsGastrointestinal stromal tumorsSolid human malignanciesRenal cell carcinomaBasic fibroblast growth factorRole of VEGFTypes of cancerFibroblast growth factorStromal tumorsTherapeutic optionsCell carcinomaColorectal cancerAntiangiogenic drugsClinical trialsDrug classesPro-angiogenic growth factorsSmall molecule inhibitorsTumor growthTumor angiogenesisMatrix breakdownDevelopment and Validation of a Drug Activity Biomarker that Shows Target Inhibition in Cancer Patients Receiving Enzastaurin, a Novel Protein Kinase C-β Inhibitor
Green LJ, Marder P, Ray C, Cook CA, Jaken S, Musib LC, Herbst RS, Carducci M, Britten CD, Basche M, Eckhardt SG, Thornton D. Development and Validation of a Drug Activity Biomarker that Shows Target Inhibition in Cancer Patients Receiving Enzastaurin, a Novel Protein Kinase C-β Inhibitor. Clinical Cancer Research 2006, 12: 3408-3415. PMID: 16740765, DOI: 10.1158/1078-0432.ccr-05-2231.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Combined Chemotherapy ProtocolsBiomarkersCapecitabineCell Line, TumorClinical Trials, Phase I as TopicDeoxycytidineEnzyme ActivatorsEnzyme InhibitorsFlow CytometryFluorouracilFollow-Up StudiesHumansIndolesLeukocytes, MononuclearMonocytesNeoplasmsProtein Kinase CProtein Kinase C betaReproducibility of ResultsSensitivity and SpecificitySignal TransductionStructure-Activity RelationshipTreatment OutcomeConceptsPeripheral blood mononuclear cellsDaily oral dosesBlood mononuclear cellsCancer patientsOral dosesMononuclear cellsFlow cytometryDrug activity biomarkerPKC activityTarget cellsActivity biomarkersPhorbol esterNormal donorsPatientsActivity of PKCU937 cell lineTarget inhibitionEnzastaurinKinase inhibitorsΒ inhibitorSignificant decreaseCell linesU937 cellsIntracellular phosphoproteinsProtein kinase C
2004
Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Does Not Improve Paclitaxel Effect in an Orthotopic Mouse Model of Lung Cancer
Onn A, Isobe T, Wu W, Itasaka S, Shintani T, Shibuya K, Kenji Y, O’Reilly M, Fidler IJ, Herbst RS. Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Does Not Improve Paclitaxel Effect in an Orthotopic Mouse Model of Lung Cancer. Clinical Cancer Research 2004, 10: 8613-8619. PMID: 15623645, DOI: 10.1158/1078-0432.ccr-04-1241.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinoma, Bronchiolo-AlveolarAnimalsAntineoplastic Agents, PhytogenicCarcinoma, Non-Small-Cell LungDrug Therapy, CombinationEnzyme ActivationEnzyme InhibitorsErbB ReceptorsFibroblast Growth Factor 2HumansLung NeoplasmsMaleMiceMice, NudeMitogen-Activated Protein KinasesModels, AnimalPaclitaxelPhosphorylationPyrimidinesPyrrolesSurvival RateConceptsEGFR tyrosine kinase inhibitorsTumor implantationLung cancerKinase inhibitorsEpidermal growth factor receptor tyrosine kinase inhibitorsGrowth factor receptor tyrosine kinase inhibitorsReceptor tyrosine kinase inhibitorsBasic fibroblast growth factor expressionCombination of paclitaxelFibroblast growth factor expressionGroups of miceLungs of miceOrthotopic mouse modelHuman lung cancerTyrosine kinase inhibitorsGrowth factor expressionMaximal therapeutic effectHuman lung adenocarcinoma cellsLung adenocarcinoma cellsPaclitaxel 100Phosphorylation of EGFRConcurrent administrationEGFR-TKITherapeutic effectEpidermal growth factor receptor (EGFR) activationEGFR inhibition in NSCLC: the emerging role of cetuximab.
Herbst RS. EGFR inhibition in NSCLC: the emerging role of cetuximab. Journal Of The National Comprehensive Cancer Network 2004, 2 Suppl 2: s41-51. PMID: 19780245.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerEpidermal growth factor receptor inhibitorsGrowth factor receptor inhibitorsCell lung cancerTyrosine kinase inhibitorsLung cancerReceptor inhibitorsKinase inhibitorsAdvanced non-small cell lung cancerMonoclonal antibodiesEpidermal growth factor receptor expressionChemotherapy-related toxicityGrowth factor receptor expressionGrowth factor receptor inhibitionRole of cetuximabPhase II trialInterstitial lung diseaseEpidermal growth factor receptor inhibitionOverall response rateFactor receptor expressionModerate rashII trialUntreated patientsHypersensitivity reactionsLung disease
2003
Gefitinib: current and future status in cancer therapy.
Herbst RS, Kies MS. Gefitinib: current and future status in cancer therapy. Clinical Advances In Hematology And Oncology 2003, 1: 466-72. PMID: 16258434.Peer-Reviewed Original ResearchConceptsEpidermal growth factor receptorTumor growthEGFR tyrosine kinase inhibitorsCurrent clinical development statusOngoing clinical trialsCombination of gefitinibClinical development statusCancer cell growthHost-dependent processesGrowth factor receptorHormonal therapyStandard chemotherapyBiologic agentsDisease recurrenceCell lungSolid malignanciesClinical trialsTumor cell functionsViable drug targetNovel agentsPreclinical studiesClinical developmentTumor typesGefitinibKinase inhibitors
2002
The role of the epidermal growth factor receptor in the treatment of colorectal carcinoma
Waxman ES, Herbst RS. The role of the epidermal growth factor receptor in the treatment of colorectal carcinoma. Seminars In Oncology Nursing 2002, 18: 20-29. PMID: 12053861, DOI: 10.1053/sonu.2002.33072.Peer-Reviewed Original ResearchConceptsEpidermal growth factor receptorColorectal carcinomaGrowth factor receptorClinical experienceAnti-EGFR monoclonal antibodiesTraditional cytotoxic approachesFactor receptorExtensive clinical testingTyrosine kinase inhibitorsEarly clinical experienceVariety of tumorsSignificant antitumor activityBiological agentsTreatment of cancerCytotoxic approachesEGFR resultsClinical testingNursing practiceCarcinomaMonoclonal antibodiesEGFR pathwayKinase inhibitorsAntitumor activityVariety of mechanismsReceptors
2001
Epidermal growth factor receptor biology (IMC-C225)
Kim E, Khuri F, Herbst R. Epidermal growth factor receptor biology (IMC-C225). Current Opinion In Oncology 2001, 13: 506-513. PMID: 11673692, DOI: 10.1097/00001622-200111000-00014.Peer-Reviewed Original ResearchConceptsIMC-C225Epidermal growth factor receptor biologyMonoclonal antibodiesLigand-linked toxinsOverall clinical outcomeOverall poor prognosisTyrosine kinase inhibitorsTyrosine kinase inhibitionOverexpression of EGFRNovel monoclonal antibodyClinical outcomesPoor prognosisTreatment of cancerRadiation therapySolid tumorsEpithelial cancersTumor proliferationEGFRGrowth factorKinase inhibitorsCancerReceptor biologyAntibodiesKinase inhibitionEGF receptor
2000
Objective regressions in non-small cell lung cancer patients treated in Phase I trials of oral ZD1839 (IressaTM), a selective tyrosine kinase inhibitor that blocks the epidermal growth factor receptor (EGFR)
Kris M, Herbst R, Rischin D, LoRusso P, Baselga J, Hammond L, Feyereislova A, Ochs J, Averbuch S. Objective regressions in non-small cell lung cancer patients treated in Phase I trials of oral ZD1839 (IressaTM), a selective tyrosine kinase inhibitor that blocks the epidermal growth factor receptor (EGFR). Lung Cancer 2000, 29: 72. DOI: 10.1016/s0169-5002(00)80233-0.Peer-Reviewed Original ResearchEpidermal growth factor receptorNon-small cell lung cancer patientsCell lung cancer patientsPhase I trialSelective tyrosine kinase inhibitorLung cancer patientsTyrosine kinase inhibitorsGrowth factor receptorObjective regressionI trialCancer patientsOral ZD1839Kinase inhibitorsFactor receptorPatientsZD1839Treatment for malignant pleural effusion of human lung adenocarcinoma by inhibition of vascular endothelial growth factor receptor tyrosine kinase phosphorylation.
Yano S, Herbst RS, Shinohara H, Knighton B, Bucana CD, Killion JJ, Wood J, Fidler IJ. Treatment for malignant pleural effusion of human lung adenocarcinoma by inhibition of vascular endothelial growth factor receptor tyrosine kinase phosphorylation. Clinical Cancer Research 2000, 6: 957-65. PMID: 10741721.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAngiogenesis InhibitorsAnimalsCapillary PermeabilityCell DivisionCell LineEndothelial Growth FactorsEndothelium, VascularGene Expression RegulationHumansImmunohistochemistryIn Situ HybridizationLung NeoplasmsLymphokinesMaleMiceMice, Inbred BALB CMice, NudeNeoplasm TransplantationNeovascularization, PathologicPhosphorylationPhthalazinesPleural Effusion, MalignantPyridinesReceptor Protein-Tyrosine KinasesReceptors, Growth FactorReceptors, Vascular Endothelial Growth FactorTransplantation, HeterologousTumor Cells, CulturedVascular Endothelial Growth Factor AVascular Endothelial Growth FactorsConceptsMalignant pleural effusionReceptor tyrosine kinase inhibitorsPleural effusionPTK 787Human dermal microvascular endothelial cellsTyrosine kinase inhibitorsPC14PE6 cellsDermal microvascular endothelial cellsMicrovascular endothelial cellsVEGF/VPFOral treatmentLung lesionsGrowth factor receptor tyrosine kinase inhibitorsAdvanced human lung cancerPlatelet-derived growth factor receptor tyrosine kinase inhibitorVEGF/VPF proteinEndothelial cellsKinase inhibitorsVascular endothelial growth factor/vascular permeability factorHuman lung cancerNude mouse modelHuman lung adenocarcinomaHuman lung adenocarcinoma cellsVascular permeability factorHuman lung carcinoma cells