2017
Stress 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 resistance
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 ICancer
2006
Phase I Dose Escalation and Pharmacokinetic Study of Enzastaurin, an Oral Protein Kinase C Beta Inhibitor, in Patients With Advanced Cancer
Carducci MA, Musib L, Kies MS, Pili R, Truong M, Brahmer JR, Cole P, Sullivan R, Riddle J, Schmidt J, Enas N, Sinha V, Thornton DE, Herbst RS. Phase I Dose Escalation and Pharmacokinetic Study of Enzastaurin, an Oral Protein Kinase C Beta Inhibitor, in Patients With Advanced Cancer. Journal Of Clinical Oncology 2006, 24: 4092-4099. PMID: 16943527, DOI: 10.1200/jco.2005.05.3447.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAdultAgedAntineoplastic AgentsDose-Response Relationship, DrugDrug Administration ScheduleFemaleFlow CytometryGene Expression Regulation, EnzymologicGene Expression Regulation, NeoplasticHumansIndolesMaleMiddle AgedNeoplasmsProtein Kinase CProtein Kinase C betaProtein Kinase InhibitorsConceptsMaximum-tolerated doseProtein kinase C beta inhibitorStable diseaseAdvanced cancerEastern Cooperative Oncology Group performance statusSignificant grade 3/4 toxicityBeta inhibitorGrade 3/4 toxicitiesPhase II dosePhase II trialDose-limiting toxicityYears of ageExpansion cohortGI toxicityII trialStarting dosePerformance statusDose escalationAdditional patientsNeck cancerPrevalent malignancySafety dataPatientsSecondary objectiveEnzastaurinDevelopment 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
2005
Current Management of Advanced Non-Small Cell Lung Cancer: Targeted Therapy
Isobe T, Herbst RS, Onn A. Current Management of Advanced Non-Small Cell Lung Cancer: Targeted Therapy. Seminars In Oncology 2005, 32: 315-328. PMID: 15988686, DOI: 10.1053/j.seminoncol.2005.02.016.Peer-Reviewed Original ResearchMeSH KeywordsAlkyl and Aryl TransferasesAngiogenesis InhibitorsAnimalsAntibodies, MonoclonalAntineoplastic AgentsCarcinoma, Non-Small-Cell LungCyclooxygenase InhibitorsDrug Delivery SystemsErbB ReceptorsFarnesyltranstransferaseHumansLung NeoplasmsMatrix Metalloproteinase InhibitorsProtein Kinase CReceptor, ErbB-2Receptors, Vascular Endothelial Growth FactorRetinoid X ReceptorsConceptsNon-small cell lung cancerAdvanced non-small cell lung cancerCell lung cancerLung cancerVascular endothelial growth factorEpidermal growth factor receptorBiological therapyGrowth factorLung cancer patientsCancer-related deathLung cancer progressionClinical study designNew therapeutic strategiesEndothelial growth factorGrowth factor receptorOverall prognosisPatient survivalStandard treatmentCancer patientsConventional chemotherapyFrequent causeRadiation therapyTherapeutic approachesAnticancer arsenalTherapeutic strategies
2002
Targeted therapy in non-small-cell lung cancer.
Herbst RS. Targeted therapy in non-small-cell lung cancer. Oncology 2002, 16: 19-24. PMID: 12375797.Peer-Reviewed Original ResearchMeSH KeywordsAngiogenesis InhibitorsAntibodies, MonoclonalAntineoplastic AgentsCarcinoma, Non-Small-Cell LungClinical Trials as TopicEndothelial Growth FactorsErbB ReceptorsHumansIntercellular Signaling Peptides and ProteinsLung NeoplasmsLymphokinesProtein Kinase CVascular Endothelial Growth Factor AVascular Endothelial Growth FactorsConceptsCell lung cancerLung cancerSuch new agentsNew agentsVascular endothelial growth factor inhibitorsPlatinum-based combination therapyEGFR tyrosine kinase inhibitorsGrowth factor receptor inhibitorsNew biologic therapiesGrowth factor inhibitorsEpithelial growth factor receptor inhibitorTyrosine kinase inhibitorsSpecific biologic pathwaysDevelopment of agentsSignal transduction inhibitorsMaintenance therapyBiologic therapyCytotoxic chemotherapyStages of treatmentFactor inhibitorsCombination therapyTargeted therapyReceptor inhibitorsRadiation therapyClinical investigation