2022
BFAST but be smart: bTMB remains an exploratory biomarker in NSCLC
Kim SY, Herbst RS. BFAST but be smart: bTMB remains an exploratory biomarker in NSCLC. Nature Reviews Clinical Oncology 2022, 20: 3-4. PMID: 36271141, DOI: 10.1038/s41571-022-00698-y.Peer-Reviewed Original ResearchConceptsCell lung cancerTumor mutational burdenLung cancerMutational burdenBlood-based tumor mutational burdenAdvanced-stage solid tumorsFirst phase III trialHigh tumor mutational burdenImmune checkpoint inhibitorsPhase III trialsIII trialsPredictive biomarkersExploratory biomarkersCompanion biomarkersSolid tumorsBiomarkersCancerBurdenPembrolizumabNSCLCPatientsTumorsTrialsAdaptive immune resistance at the tumour site: mechanisms and therapeutic opportunities
Kim TK, Vandsemb EN, Herbst RS, Chen L. Adaptive immune resistance at the tumour site: mechanisms and therapeutic opportunities. Nature Reviews Drug Discovery 2022, 21: 529-540. PMID: 35701637, DOI: 10.1038/s41573-022-00493-5.Peer-Reviewed Original ResearchConceptsAdaptive immune resistanceImmune resistanceCell death 1 ligand 1Tumor siteDeath 1 ligand 1Anti-PD therapyBlockade of PDL1Advanced-stage cancerFraction of patientsStrong mechanistic rationaleFuture drug developmentCurrent cancer therapiesImmune attackClinical trialsSolid tumorsTherapeutic opportunitiesTumorsCancer therapySelective inductionAntitumour drugsLigand 1Drug developmentTherapyAdditive effectMechanistic rationale
2020
Comprehensive T cell repertoire characterization of non-small cell lung cancer
Reuben A, Zhang J, Chiou SH, Gittelman RM, Li J, Lee WC, Fujimoto J, Behrens C, Liu X, Wang F, Quek K, Wang C, Kheradmand F, Chen R, Chow CW, Lin H, Bernatchez C, Jalali A, Hu X, Wu CJ, Eterovic AK, Parra ER, Yusko E, Emerson R, Benzeno S, Vignali M, Wu X, Ye Y, Little LD, Gumbs C, Mao X, Song X, Tippen S, Thornton RL, Cascone T, Snyder A, Wargo JA, Herbst R, Swisher S, Kadara H, Moran C, Kalhor N, Zhang J, Scheet P, Vaporciyan AA, Sepesi B, Gibbons DL, Robins H, Hwu P, Heymach JV, Sharma P, Allison JP, Baladandayuthapani V, Lee JJ, Davis MM, Wistuba II, Futreal PA, Zhang J. Comprehensive T cell repertoire characterization of non-small cell lung cancer. Nature Communications 2020, 11: 603. PMID: 32001676, PMCID: PMC6992630, DOI: 10.1038/s41467-019-14273-0.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerCell lung cancerT cellsLung cancerAdoptive T-cell therapyEarly-stage NSCLC patientsT cell repertoire analysisT cell responsesLungs of patientsT-cell therapyNSCLC patientsInferior survivalClinicopathologic featuresImmune landscapeViral infectionSolid tumorsTherapeutic efficacyCell responsesCell therapyPatientsRepertoire analysisLungTumorsImmunotherapyConsiderable proportion
2017
Impaired HLA Class I Antigen Processing and Presentation as a Mechanism of Acquired Resistance to Immune Checkpoint Inhibitors in Lung Cancer
Gettinger S, Choi J, Hastings K, Truini A, Datar I, Sowell R, Wurtz A, Dong W, Cai G, Melnick MA, Du VY, Schlessinger J, Goldberg SB, Chiang A, Sanmamed MF, Melero I, Agorreta J, Montuenga LM, Lifton R, Ferrone S, Kavathas P, Rimm DL, Kaech SM, Schalper K, Herbst RS, Politi K. Impaired HLA Class I Antigen Processing and Presentation as a Mechanism of Acquired Resistance to Immune Checkpoint Inhibitors in Lung Cancer. Cancer Discovery 2017, 7: cd-17-0593. PMID: 29025772, PMCID: PMC5718941, DOI: 10.1158/2159-8290.cd-17-0593.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsPatient-derived xenograftsHLA class ILung cancerClass ICell surface HLA class ILung cancer mouse modelPD-1 blockadeStandard treatment algorithmCancer mouse modelLung cancer samplesDefective antigen processingCheckpoint inhibitorsPD-1Treatment algorithmMouse modelAntagonistic antibodiesDiverse malignanciesAntigen processingCancer samplesB2MHomozygous lossTumorsCancerRecurrent mutations
2016
P2.41 (also presented as PD1.06): Pembrolizumab vs Docetaxel for Previously Treated NSCLC (KEYNOTE-010): Archival vs New Tumor Samples for PD-L1 Assessment Track: Immunotherapy
Herbst R, Baas P, Perez-Gracia J, Felip E, Kim D, Han J, Molina J, Kim J, Arvis C, Ahn M, Majem M, Fidler M, Surmont V, De Castro G, Garrido M, Shentu Y, Dolled-Filhart M, Im E, Garon E. P2.41 (also presented as PD1.06): Pembrolizumab vs Docetaxel for Previously Treated NSCLC (KEYNOTE-010): Archival vs New Tumor Samples for PD-L1 Assessment Track: Immunotherapy. Journal Of Thoracic Oncology 2016, 11: s242-s243. DOI: 10.1016/j.jtho.2016.08.112.Peer-Reviewed Original Research
2015
Targeted Therapy in Solid Tumors: Lung Cancer
Waqar S, Morgensztern D, Herbst R. Targeted Therapy in Solid Tumors: Lung Cancer. 2015, 224-230. DOI: 10.1002/9781118468678.ch23.Peer-Reviewed Original ResearchNon-small cell lung cancerLung cancerManagement of NSCLCMetastatic non-small cell lung cancerChoice of regimensUnprecedented response ratesProgression-free survivalEarly-stage diseaseIncurable metastatic diseaseCell lung cancerImproved cure ratesToxic treatment optionsMetastatic diseaseStage diseaseCure rateTreatment optionsTargeted therapyToxicity profileSecondary resistanceResponse rateSolid tumorsPatientsTumor progressionTherapyTumorsCo-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 molecules
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 AdultNew Strategies in Personalized Medicine for Solid Tumors: Molecular Markers and Clinical Trial Designs
Jürgensmeier JM, Eder JP, Herbst RS. New Strategies in Personalized Medicine for Solid Tumors: Molecular Markers and Clinical Trial Designs. Clinical Cancer Research 2014, 20: 4425-4435. PMID: 25183480, PMCID: PMC5369358, DOI: 10.1158/1078-0432.ccr-13-0753.Peer-Reviewed Original ResearchConceptsClinical trialsTumor biologyFuture patient selectionTherapy of patientsOngoing clinical evaluationBroad molecular profilingPromising tumor targetPersonalized medicinePatient selectionPatient populationTreatment recommendationsClinical evaluationTumor boardClinical studiesImmune parametersNovel agentsTumor targetsTreatment approachesSolid tumorsClinical researchPatientsMolecular profilingSpecific markersTumorsTrialsA phase I/II, first-in-human dose-escalation study of GSK2636771 in patients (pts) with PTEN-deficient advanced tumors.
Arkenau H, Mateo J, Lemech C, Infante J, Burris H, Bang Y, Eder J, Herbst R, Sharma S, Chung H, Decordova S, Swales K, Garrett M, Loftiss J, Durante M, Russo M, Suttle B, Motwani M, Kumar R, De Bono J. A phase I/II, first-in-human dose-escalation study of GSK2636771 in patients (pts) with PTEN-deficient advanced tumors. Journal Of Clinical Oncology 2014, 32: 2514-2514. DOI: 10.1200/jco.2014.32.15_suppl.2514.Peer-Reviewed Original Research
2012
Targeting the Apoptotic Pathway in Chondrosarcoma Using Recombinant Human Apo2L/TRAIL (Dulanermin), a Dual Proapoptotic Receptor (DR4/DR5) Agonist
Subbiah V, Brown RE, Buryanek J, Trent J, Ashkenazi A, Herbst R, Kurzrock R. Targeting the Apoptotic Pathway in Chondrosarcoma Using Recombinant Human Apo2L/TRAIL (Dulanermin), a Dual Proapoptotic Receptor (DR4/DR5) Agonist. Molecular Cancer Therapeutics 2012, 11: 2541-2546. PMID: 22914439, PMCID: PMC3496030, DOI: 10.1158/1535-7163.mct-12-0358.Peer-Reviewed Original ResearchMeSH KeywordsApoptosisBone NeoplasmsCell SurvivalChondrosarcomaDNA Mutational AnalysisHumansImmunohistochemistryIsocitrate DehydrogenaseLung NeoplasmsMaleMiddle AgedProteomicsProto-Oncogene Proteins c-bcl-2Radiography, ThoracicReceptors, Death DomainRecombinant ProteinsSignal TransductionTNF-Related Apoptosis-Inducing LigandTomography, X-Ray ComputedTreatment OutcomeConceptsRecombinant human Apo2L/TRAILApo2L/TRAILRecent computed tomography scanSustained partial responseEvidence of diseaseComputed tomography scanP-ERK 1/2Partial responseProgressive diseaseNF-κBp65Receptor agonistTomography scanSubcentimeter nodulesPatient tumorsMetastatic chondrosarcomaP-mTORPatientsProlonged responseP-STAT3Proapoptotic receptor agonistsChondrosarcomaBcl-2DulanerminLungTumorsReports from the 2010 Clinical and Translational Cancer Research Think Tank Meeting: Design Strategies for Personalized Therapy Trials
Berry DA, Herbst RS, Rubin EH. Reports from the 2010 Clinical and Translational Cancer Research Think Tank Meeting: Design Strategies for Personalized Therapy Trials. Clinical Cancer Research 2012, 18: 638-644. PMID: 22298897, PMCID: PMC4314693, DOI: 10.1158/1078-0432.ccr-11-2018.Peer-Reviewed Original ResearchConceptsClinical trialsMajority of patientsSingle-therapy approachesSame histologyTranslational cancer researchSingle therapyHeterogeneous diseaseCertain therapiesClinical strategiesPatientsTherapy trialsTherapyClinical researchTrialsTank meetingDiseaseClinical experimentsAdaptive trialsBiomarker subsetsCancer researchSubsetOvertreatmentClinicalHistologyTumors
2011
Evaluation of pharmacodynamic biomarkers in a Phase 1a trial of dulanermin (rhApo2L/TRAIL) in patients with advanced tumours
Pan Y, Xu R, Peach M, Huang CP, Branstetter D, Novotny W, Herbst RS, Eckhardt SG, Holland PM. Evaluation of pharmacodynamic biomarkers in a Phase 1a trial of dulanermin (rhApo2L/TRAIL) in patients with advanced tumours. British Journal Of Cancer 2011, 105: 1830-1838. PMID: 22033270, PMCID: PMC3251880, DOI: 10.1038/bjc.2011.456.Peer-Reviewed Original ResearchConceptsCell death markersAdvanced tumorsPharmacodynamic biomarkersApoptotic markersPhase 1a studyPhase 1a trialDeath receptors DR4Colo205 tumorsSerum 8Patients 24Active caspase-3Patient seraColo205 xenograftsEvidence of activitySubsequent cell deathCytokeratin 18PatientsTransient increaseDulanerminReceptors DR4TumorsCaspase-3SerumCaspase-3/7Significant increase
2010
First-in-human phase I study of the oral PI3K inhibitor BEZ235 in patients (pts) with advanced solid tumors.
Burris H, Rodon J, Sharma S, Herbst R, Tabernero J, Infante J, Silva A, Demanse D, Hackl W, Baselga J. First-in-human phase I study of the oral PI3K inhibitor BEZ235 in patients (pts) with advanced solid tumors. Journal Of Clinical Oncology 2010, 28: 3005-3005. DOI: 10.1200/jco.2010.28.15_suppl.3005.Peer-Reviewed Original ResearchMolecular Pharmacology and Antitumor Activity of PHT-427, a Novel Akt/Phosphatidylinositide-Dependent Protein Kinase 1 Pleckstrin Homology Domain Inhibitor
Meuillet EJ, Zuohe S, Lemos R, Ihle N, Kingston J, Watkins R, Moses SA, Zhang S, Du-Cuny L, Herbst R, Jacoby JJ, Zhou LL, Ahad AM, Mash EA, Kirkpatrick DL, Powis G. Molecular Pharmacology and Antitumor Activity of PHT-427, a Novel Akt/Phosphatidylinositide-Dependent Protein Kinase 1 Pleckstrin Homology Domain Inhibitor. Molecular Cancer Therapeutics 2010, 9: 706-717. PMID: 20197390, PMCID: PMC2837366, DOI: 10.1158/1535-7163.mct-09-0985.Peer-Reviewed Original ResearchMeSH Keywords3-Phosphoinositide-Dependent Protein KinasesAnimalsAntineoplastic AgentsFemaleHumansMiceMice, Inbred C57BLMice, NudeModels, BiologicalOncogene Protein v-aktProtein BindingProtein Interaction Domains and MotifsProtein Kinase InhibitorsProtein Serine-Threonine KinasesSulfonamidesThiadiazolesTumor Cells, CulturedXenograft Model Antitumor AssaysConceptsAntitumor activityTumor xenograftsNon-small cell lung cancerMolecular pharmacologyCell lung cancerAdditive antitumor activityHuman tumor xenograftsPHT-427K-ras mutant tumorsVivo antitumor activityLung cancerSensitive tumorsPIK3CA mutationsBreast cancerImmunodeficient miceBlood chemistryMutant tumorsCombination studiesResistant cellsMinimal toxicityWeight lossTumorsCancerCancer cellsAkt inhibition
2009
Targeted drug delivery strategies to treat lung metastasis
Bar J, Herbst RS, Onn A. Targeted drug delivery strategies to treat lung metastasis. Expert Opinion On Drug Delivery 2009, 6: 1003-1016. PMID: 19663628, DOI: 10.1517/17425240903167926.Peer-Reviewed Original ResearchConceptsLung metastasesStandard clinical useMetastatic diseaseClinical trialsClinical useMost cancer patientsEarly clinical studiesCancer-specific antibodiesDrug delivery strategiesMain tumorTargeted drug delivery strategiesCancer patientsClinical studiesIntravascular devicesSolid tumorsMetastasisPreclinical developmentVascular fieldTreatmentTherapyTumorsAnticancer toolDiseaseDelivery strategiesTrialsSummary of Selected Presentations from the 8th Annual Targeted Therapy in Lung Cancer Symposium
Camidge R, Gaspar L, Goss G, Kelly K, Ramalingam S, Reckamp K, Simon G, Tsao M, West H, Herbst R, Johnson D, Bunn P, Govindan R. Summary of Selected Presentations from the 8th Annual Targeted Therapy in Lung Cancer Symposium. Journal Of Thoracic Oncology 2009, 4: 930-935. PMID: 19550249, DOI: 10.1097/jto.0b013e3181a9a03b.Peer-Reviewed Original ResearchConceptsLung cancerTargeted therapyGastrointestinal stromal tumorsCancer-related deathChronic myeloid leukemiaCancer SymposiumCytotoxic chemotherapyStromal tumorsMyeloid leukemiaBreast cancerCancerTherapyMolecular targetsCancer therapyTreatmentStriking improvementConsiderable optimismAnnual MeetingCancer genomicsChemotherapyInternational AssociationPatientsLeukemiaTumorsYearsTumor Blood Flow Measured by Perfusion Computed Tomography and 15O-Labeled Water Positron Emission Tomography
Ng CS, Kodama Y, Mullani NA, Barron BJ, Wei W, Herbst RS, Abbruzzese JL, Charnsangavej C. Tumor Blood Flow Measured by Perfusion Computed Tomography and 15O-Labeled Water Positron Emission Tomography. Journal Of Computer Assisted Tomography 2009, 33: 460-465. PMID: 19478644, DOI: 10.1097/rct.0b013e318182d2e0.Peer-Reviewed Original ResearchConceptsWater positron emission tomographyPositron emission tomographyBlood flowEmission tomographyMean blood flow valuesBlood flow estimatesPerfusion Computed TomographyTumor blood flowPairs of examinationsBlood flow valuesMixed regression analysesUse of PCTBlood flow measurementsClinical gold standardIndex tumorClinical studiesComputed tomographySolid tumorsTumorsGold standardBland-AltmanTomographySignificant differencesRegression analysisT-test
2008
Phase I multicenter trial of BMS-690514: Safety, pharmacokinetic profile, biological effects, and early clinical evaluation in patients with advanced solid tumors and non-small cell lung cancer
Bahleda R, Felip E, Herbst R, Hanna N, Laurie S, Shepherd F, Armand J, Sweeney C, Calvo-Aller E, Soria J. Phase I multicenter trial of BMS-690514: Safety, pharmacokinetic profile, biological effects, and early clinical evaluation in patients with advanced solid tumors and non-small cell lung cancer. Journal Of Clinical Oncology 2008, 26: 2564-2564. DOI: 10.1200/jco.2008.26.15_suppl.2564.Peer-Reviewed Original ResearchClinical, pharmacokinetic (PK), pharmacodynamic findings in a phase I trial of weekly (wkly) intravenous AZD4877 in patients with refractory solid tumors
Infante J, Spratlin J, Kurzrock R, Eckhardt S, Burris H, Puchalski T, Li J, Wu K, Ochs J, Herbst R. Clinical, pharmacokinetic (PK), pharmacodynamic findings in a phase I trial of weekly (wkly) intravenous AZD4877 in patients with refractory solid tumors. Journal Of Clinical Oncology 2008, 26: 2501-2501. DOI: 10.1200/jco.2008.26.15_suppl.2501.Peer-Reviewed Original Research