2019
PTEN loss is associated with resistance to cetuximab in patients with head and neck squamous cell carcinoma
Eze N, Lee JW, Yang DH, Zhu F, Neumeister V, Sandoval-Schaefer T, Mehra R, Ridge JA, Forastiere A, Chung CH, Burtness B. PTEN loss is associated with resistance to cetuximab in patients with head and neck squamous cell carcinoma. Oral Oncology 2019, 91: 69-78. PMID: 30926065, PMCID: PMC6855599, DOI: 10.1016/j.oraloncology.2019.02.026.Peer-Reviewed Original ResearchConceptsNeck squamous cell carcinomaEpidermal growth factor receptorSquamous cell carcinomaCell carcinomaCetuximab-based therapyTrial of cisplatinTrials (RCTs) of cetuximabPotential predictive biomarkersPTEN expressionLack of benefitPI3K mutationsPI3K p110αHigh PTEN expressionPI3K pathwayGrowth factor receptorHot spot mutationsStandard therapySuperior PFSMultivariable analysisPredictive biomarkersLoss of expressionSuch therapyCommon abnormalityCetuximabSide effects
2016
EGFR and RB1 as Dual Biomarkers in HPV-Negative Head and Neck Cancer
Beck TN, Georgopoulos R, Shagisultanova EI, Sarcu D, Handorf EA, Dubyk C, Lango MN, Ridge JA, Astsaturov I, Serebriiskii IG, Burtness BA, Mehra R, Golemis EA. EGFR and RB1 as Dual Biomarkers in HPV-Negative Head and Neck Cancer. Molecular Cancer Therapeutics 2016, 15: 2486-2497. PMID: 27507850, PMCID: PMC5522587, DOI: 10.1158/1535-7163.mct-16-0243.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overBiomarkers, TumorCyclin-Dependent Kinase 4Cyclin-Dependent Kinase 6ErbB ReceptorsFemaleHead and Neck NeoplasmsHumansImmunohistochemistryKaplan-Meier EstimateMaleMiddle AgedModels, BiologicalNeoplasm StagingPapillomaviridaePapillomavirus InfectionsPhosphorylationPrognosisProtein Kinase InhibitorsReceptor, ErbB-2Retinoblastoma Binding ProteinsUbiquitin-Protein LigasesConceptsEpidermal growth factor receptorRetinoblastoma 1Neck squamous cell carcinomaExpression of EGFRSquamous cell carcinomaCDK4/6 inhibitor palbociclibSignificant survival differenceResponse predictive biomarkersHPV-negative HNSCCHigh epidermal growth factor receptorStratification of casesImportant therapeutic targetSynergistic inhibitory effectGrowth factor receptorCell cycle modulatorsCell carcinomaDisease stageInhibitor palbociclibHuman papillomavirusSurvival differencesHNSCC samplesTherapeutic decisionsHNSCC cellsAnatomic locationDrug combinations
2015
A Phase I Study of CUDC-101, a Multitarget Inhibitor of HDACs, EGFR, and HER2, in Combination with Chemoradiation in Patients with Head and Neck Squamous Cell Carcinoma
Galloway TJ, Wirth LJ, Colevas AD, Gilbert J, Bauman JE, Saba NF, Raben D, Mehra R, W. A, Atoyan R, Wang J, Burtness B, Jimeno A. A Phase I Study of CUDC-101, a Multitarget Inhibitor of HDACs, EGFR, and HER2, in Combination with Chemoradiation in Patients with Head and Neck Squamous Cell Carcinoma. Clinical Cancer Research 2015, 21: 1566-1573. PMID: 25573383, PMCID: PMC6607903, DOI: 10.1158/1078-0432.ccr-14-2820.Peer-Reviewed Original ResearchConceptsHuman growth factor receptor 2Peripheral blood mononuclear cellsEpidermal growth factor receptorDose-limiting toxicityAdverse eventsCUDC-101Tumor biopsiesHistone deacetylaseNeck squamous cell cancerNeck squamous cell carcinomaHigh-risk HNSCCGrowth factor receptor 2Squamous cell cancerSquamous cell carcinomaBlood mononuclear cellsExternal beam radiationTreatment of HNSCCRoute of administrationOne-week runFactor receptor 2Concurrent cisplatinGrowth factor receptorRisk patientsCell cancerCell carcinomaEGFR-directed antibodies increase the risk of severe infection in cancer patients
Altan M, Burtness B. EGFR-directed antibodies increase the risk of severe infection in cancer patients. BMC Medicine 2015, 13: 37. PMID: 25857245, PMCID: PMC4336483, DOI: 10.1186/s12916-015-0276-9.Peer-Reviewed Original ResearchConceptsEpidermal growth factor receptorSevere infectionsMonoclonal antibodiesRole of EGFRDose modification strategiesMonoclonal antibody treatmentClinical trial designRisk of infectionPractice of oncologyGrowth factor receptorConstitutional symptomsAntibody treatmentHypersensitivity reactionsCancer patientsRadiation therapyTrial designSolid tumorsInfection riskInfectionFactor receptorAntibodiesFurther studiesPatientsRiskRelated articles
2014
Afatinib versus placebo as adjuvant therapy after chemoradiation in a double-blind, phase III study (LUX-Head & Neck 2) in patients with primary unresected, clinically intermediate-to-high-risk head and neck cancer: study protocol for a randomized controlled trial
Burtness B, Bourhis JP, Vermorken JB, Harrington KJ, Cohen E. Afatinib versus placebo as adjuvant therapy after chemoradiation in a double-blind, phase III study (LUX-Head & Neck 2) in patients with primary unresected, clinically intermediate-to-high-risk head and neck cancer: study protocol for a randomized controlled trial. Trials 2014, 15: 469. PMID: 25432788, PMCID: PMC4289298, DOI: 10.1186/1745-6215-15-469.Peer-Reviewed Original ResearchMeSH KeywordsAfatinibAntineoplastic AgentsCarcinoma, Squamous CellChemoradiotherapyChemotherapy, AdjuvantClinical ProtocolsDisease-Free SurvivalDouble-Blind MethodErbB ReceptorsHead and Neck NeoplasmsHumansMolecular Targeted TherapyNeoplasm Recurrence, LocalNeoplasm StagingProtein Kinase InhibitorsQuality of LifeQuinazolinesResearch DesignRisk FactorsSquamous Cell Carcinoma of Head and NeckTime FactorsTreatment OutcomeConceptsEpidermal growth factor receptorDisease-free survivalErbB family membersAdvanced diseaseOropharynx cancerOverall survivalEndpoint measuresUnfavourable riskPrimary siteHigh-risk HNSCC patientsHPV-positive oropharynx cancerIrreversible ErbB family blockerDisease-free survival ratesRandomized phase II trialNeck squamous cell carcinomaErbB family blockerHigh-risk headHigh-risk HNSCCPrimary endpoint measureGood clinical conditionEvidence of diseaseLymph node involvementPhase II trialPhase III studyUnacceptable adverse events
2013
Esophageal carcinoma
Boland PM, Burtness B. Esophageal carcinoma. Current Opinion In Oncology 2013, 25: 417-424. PMID: 23680713, DOI: 10.1097/cco.0b013e328362105e.Peer-Reviewed Original ResearchConceptsEsophageal cancerT-lymphocyte antigen-4Platinum-based regimensSubgroup of patientsVascular endothelial growth factorGrowth factor 1 receptorImproved patient selectionEndothelial growth factorEpidermal growth factor receptorMinimal additional benefitFactor 1 receptorProminent molecular targetsGrowth factor receptorStandard cytotoxicChemotherapeutic regimenSurvival benefitPatient selectionEsophagogastric junctionTherapeutic regimensAntigen-4Esophageal carcinomaClinical investigationEncouraging dataMulticenter effortsEarly benefits
2012
Comment on “Epidermal Growth Factor Receptor Is Essential for Toll-Like Receptor 3 Signaling”
Burtness B, Marur S, Bauman JE, Golemis EA, Mehra R, Cohen SJ. Comment on “Epidermal Growth Factor Receptor Is Essential for Toll-Like Receptor 3 Signaling”. Science Signaling 2012, 5: lc5. PMID: 23233526, DOI: 10.1126/scisignal.2003734.Peer-Reviewed Original ResearchConceptsEpidermal growth factor receptorGrowth factor receptorToll-like receptor 3Functional innate immune responseFactor receptorInnate immune responseFulminant infectionCombination therapyImmune responseTumor growthReceptor 3Mammalian targetCancer therapeuticsReceptorsMTORPatientsBody of literatureTherapyTumorsInfectionNuclear epidermal growth factor receptor and p16 expression in head and neck squamous cell carcinoma
Husain H, Psyrri A, Markovic A, Rampias T, Pectasides E, Wang H, Slebos R, Yarbrough WG, Burtness B, Chung CH. Nuclear epidermal growth factor receptor and p16 expression in head and neck squamous cell carcinoma. The Laryngoscope 2012, 122: 2762-2768. PMID: 23086695, PMCID: PMC3574977, DOI: 10.1002/lary.23647.Peer-Reviewed Original ResearchConceptsEpidermal growth factor receptorNeck squamous cell carcinomaSquamous cell carcinomaP16 expressionGrowth factor receptorPrognostic factorsCell carcinomaNuclear epidermal growth factor receptorEGFR expressionP16-positive tumorsFactor receptorP16-negative tumorsStrong prognostic factorP16 levelsAvailable clinical dataHigh EGFR expressionP16 statusHNSCC tumorsOropharyngeal subsitesClinical dataImmunohistochemical stainingTissue microarrayUMSCC47More DNA damagePatients59IN Strategies to Optimize EGFR Therapies
Burtness B. 59IN Strategies to Optimize EGFR Therapies. Annals Of Oncology 2012, 23: ix42. DOI: 10.1016/s0923-7534(20)32673-9.Peer-Reviewed Original ResearchRecurrent/metastatic diseaseCombination of cetuximabCetuximab resistanceKinase inhibitorsMetastatic diseaseNeck cancerNuclear translocationInternational phase III trialReceptor tyrosine kinasesPhase III trialsSquamous cell carcinomaAugmentation of responsesDe novo resistanceH-ras mutationsMonoclonal antibody cetuximabTyrosine kinase inhibitorsK-ras mutationsFirst kinase inhibitorEpidermal growth factor receptorBristol-Myers SquibbGrowth factor receptorAdvanced headEGFR/HER2III trialsOral agentsA Phase II Study of Capecitabine, Oxaliplatin, and Cetuximab with or Without Bevacizumab as Frontline Therapy for Metastatic Colorectal Cancer. A Fox Chase Extramural Research Study
Dotan E, Meropol NJ, Burtness B, Denlinger CS, Lee J, Mintzer D, Zhu F, Ruth K, Tuttle H, Sylvester J, Cohen SJ. A Phase II Study of Capecitabine, Oxaliplatin, and Cetuximab with or Without Bevacizumab as Frontline Therapy for Metastatic Colorectal Cancer. A Fox Chase Extramural Research Study. Journal Of Gastrointestinal Cancer 2012, 43: 562-569. PMID: 22294255, PMCID: PMC3400721, DOI: 10.1007/s12029-012-9368-3.Peer-Reviewed Original ResearchConceptsVascular endothelial growth factorMetastatic colorectal cancerPhase II studyEpidermal growth factor receptorDay 1Arm B.II studyOverall survivalArm AColorectal cancerResponse rateMetastatic colorectal cancer patientsDual antibody therapySafety of capecitabineResultsTwenty-three patientsFirst-line treatmentColorectal cancer patientsOverall response rateKRAS mutation statusEndothelial growth factorBevacizumab 7.5Capecitabine 850Cetuximab 400Growth factor receptorOxaliplatin 130
2009
Treatment of pancreatic cancer with epidermal growth factor receptor-targeted therapy
Faller BA, Burtness B. Treatment of pancreatic cancer with epidermal growth factor receptor-targeted therapy. Biologics: Targets And Therapy 2009, Volume 3: 419-428. PMID: 19774209, PMCID: PMC2747340, DOI: 10.2147/btt.s3170.Peer-Reviewed Original ResearchEpidermal growth factor receptorPancreatic cancerAdvanced diseaseEpidermal growth factor receptor-targeted therapyDevelopment of rashFirst-line agentsAppropriate patient selectionReceptor-targeted therapyEGFR inhibitor erlotinibInduction of angiogenesisGrowth factor receptorSurvival benefitPatient selectionCommon malignancyPredictive factorsAvailable therapiesPancreatic adenocarcinomaClinical trialsInhibitor erlotinibLimited efficacyTreatment efficacyUnquestioned roleTumor proliferationTherapyPreclinical research
2008
The role of cetuximab for the treatment of squamous cell carcinoma of the head and neck.
Mehra R, Cohen RB, Burtness BA. The role of cetuximab for the treatment of squamous cell carcinoma of the head and neck. Clinical Advances In Hematology And Oncology 2008, 6: 742-50. PMID: 18997665, PMCID: PMC2745918.Peer-Reviewed Original ResearchConceptsRecurrent/metastatic diseaseRole of cetuximabSquamous cell carcinomaTreatment of HNSCCEpidermal growth factor receptorMetastatic diseaseCell carcinomaFirst-line regimenStandard of careGrowth factor receptorSurvival benefitSignificant morbidityCurable diseaseClinical trialsSingle agentDrug AdministrationCetuximabEGFR inhibitorsHNSCCBeneficial effectsDiseaseMonoclonal antibodiesFactor receptorCarcinomaFollowing review
2007
Clinical use of monoclonal antibodies to the epidermal growth factor receptor in colorectal cancer.
Burtness B. Clinical use of monoclonal antibodies to the epidermal growth factor receptor in colorectal cancer. Oncology 2007, 21: 964-70; discussion 970, 974, 976-7. PMID: 17715697.Peer-Reviewed Original ResearchConceptsEpidermal growth factor receptorColorectal cancerGrowth factor receptorChemotherapy-refractory colorectal cancerMonoclonal antibodiesFront-line therapyUse of cetuximabFactor receptorPredictors of responseClinical useCancerPromising novelPanitumumabSuch agentsTherapyAntibodiesReceptorsCetuximabAgentsDiseaseGene copy number of epidermal growth factor receptor (EGFR) by fluorescent in situ hybridization (FISH) in head and neck squamous cell carcinomas (HNSCC) is closely correlated with EGFR protein levels assessed by automated quantitative protein analysis (AQUA)
Weinberger P, Psyrri A, Kountourakis P, Rampias T, Sasaki C, Sasaki C, Haffty B, Kowalski D, Fountzilas G, Rimm D, Burtness B. Gene copy number of epidermal growth factor receptor (EGFR) by fluorescent in situ hybridization (FISH) in head and neck squamous cell carcinomas (HNSCC) is closely correlated with EGFR protein levels assessed by automated quantitative protein analysis (AQUA). Journal Of Clinical Oncology 2007, 25: 6023-6023. DOI: 10.1200/jco.2007.25.18_suppl.6023.Peer-Reviewed Original ResearchGene copy numberEpidermal growth factor receptorCopy numberProtein expressionSitu hybridizationProtein levelsEGFR protein levelsEGFR gene copy numberEGFR protein overexpressionQuantitative protein analysisSubcellular localizationProteomic analysisGrowth factor receptorProtein contentEGFR protein expressionProtein analysisHer signaling in pancreatic cancer
Burtness B. Her signaling in pancreatic cancer. Expert Opinion On Biological Therapy 2007, 7: 823-829. PMID: 17555368, DOI: 10.1517/14712598.7.6.823.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntimetabolites, AntineoplasticAntineoplastic Combined Chemotherapy ProtocolsCetuximabDeoxycytidineEpidermal Growth FactorErlotinib HydrochlorideGemcitabineHumansLapatinibOrganoplatinum CompoundsOxaliplatinPancreatic NeoplasmsProtein Kinase InhibitorsQuinazolinesReceptor, ErbB-2Signal TransductionTreatment OutcomeConceptsPhase II trialPhase III trialsPancreatic cancerEpidermal growth factor receptorII trialIII trialsRandomized phase II trialTreatment-refractory cancerManagement of patientsPhase I trialEGFR antibody cetuximabAddition of erlotinibGrowth factor receptorGemcitabine chemotherapyMedian survivalStandard therapyI trialPatient selectionSignificant prolongationMetastatic cancerAntibody cetuximabTherapeutic targetGemcitabineEGFR/Cancer
2005
Phase III Randomized Trial of Cisplatin Plus Placebo Compared With Cisplatin Plus Cetuximab in Metastatic/Recurrent Head and Neck Cancer: An Eastern Cooperative Oncology Group Study
Burtness B, Goldwasser MA, Flood W, Mattar B, Forastiere AA. Phase III Randomized Trial of Cisplatin Plus Placebo Compared With Cisplatin Plus Cetuximab in Metastatic/Recurrent Head and Neck Cancer: An Eastern Cooperative Oncology Group Study. Journal Of Clinical Oncology 2005, 23: 8646-8654. PMID: 16314626, DOI: 10.1200/jco.2005.02.4646.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Squamous CellCetuximabCisplatinCross-Over StudiesDose-Response Relationship, DrugDrug HypersensitivityErbB ReceptorsFemaleFollow-Up StudiesHead and Neck NeoplasmsHematologic DiseasesHumansImmunohistochemistryMaleMiddle AgedNeoplasm MetastasisNeoplasm Recurrence, LocalSeverity of Illness IndexSkin DiseasesSurvival AnalysisTime FactorsTreatment OutcomeConceptsProgression-free survivalAddition of cetuximabRecurrent/metastatic squamous cell carcinomaMedian progression-free survivalMetastatic squamous cell carcinomaEpidermal growth factor receptorSquamous cell carcinomaOverall survivalArm BArm AResponse rateEnd pointHazard ratioCell carcinomaCorrelation of EGFREastern Cooperative Oncology Group StudyMetastatic/recurrent headPhase III randomized trialsCetuximab-treated patientsMedian overall survivalObjective response ratePrimary end pointSecondary end pointsClinical end pointsDevelopment of rashRemarkably High Frequency of EGFR Expression in Breast Carcinomas with Squamous Differentiation
Bossuyt V, Fadare O, Martel M, Ocal IT, Burtness B, Moinfar F, Leibl S, Tavassoli FA. Remarkably High Frequency of EGFR Expression in Breast Carcinomas with Squamous Differentiation. International Journal Of Surgical Pathology 2005, 13: 319-327. PMID: 16273187, DOI: 10.1177/106689690501300403.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedBone NeoplasmsBreast NeoplasmsCarcinoma, AdenosquamousCarcinoma, Squamous CellCarcinosarcomaCell DifferentiationErbB ReceptorsFollow-Up StudiesHumansImmunohistochemistryKeratinsLung NeoplasmsLymph NodesLymphatic MetastasisMiddle AgedNeoplasm StagingReceptor, ErbB-2Receptors, EstrogenConceptsEpidermal growth factor receptorDisease-free survivalSquamous differentiationBreast carcinomaEstrogen receptorLymph nodesHER2 statusTissue microarrayEGFR expressionFull axillary lymph node dissectionAxillary lymph node dissectionLymph node positive breast carcinomaNode-positive breast carcinomaHuman epidermal growth factor receptorEGFR-negative tumorsLymph node dissectionPositive lymph nodesLymph node statusPositive breast carcinomaEGFR-positive tumorsEGFR-positive tumor cellsGrowth factor receptorNode dissectionEGFR positivityDistant metastasisQuantitative Determination of Nuclear and Cytoplasmic Epidermal Growth Factor Receptor Expression in Oropharyngeal Squamous Cell Cancer by Using Automated Quantitative Analysis
Psyrri A, Yu Z, Weinberger PM, Sasaki C, Haffty B, Camp R, Rimm D, Burtness BA. Quantitative Determination of Nuclear and Cytoplasmic Epidermal Growth Factor Receptor Expression in Oropharyngeal Squamous Cell Cancer by Using Automated Quantitative Analysis. Clinical Cancer Research 2005, 11: 5856-5862. PMID: 16115926, DOI: 10.1158/1078-0432.ccr-05-0420.Peer-Reviewed Original ResearchConceptsEpidermal growth factor receptorOropharyngeal squamous cell cancerLocal recurrence rateSquamous cell cancerEGFR expression levelsEGFR expressionCell cancerRecurrence rateEGFR levelsHigh tumorInferior disease-free survivalExpression levelsNeck squamous cell carcinomaEpidermal growth factor receptor expressionTumor EGFR levelsGrowth factor receptor expressionProtein expressionDisease-free survivalOropharyngeal cancer casesSquamous cell carcinomaFactor receptor expressionMedian expression levelCy5-conjugated antibodiesEGFR protein expressionNuclear EGFR levelsThe role of cetuximab in the treatment of squamous cell cancer of the head and neck
Burtness B. The role of cetuximab in the treatment of squamous cell cancer of the head and neck. Expert Opinion On Biological Therapy 2005, 5: 1085-1093. PMID: 16050785, DOI: 10.1517/14712598.5.8.1085.Peer-Reviewed Original ResearchConceptsEpidermal growth factor receptorEpidermal growth factorGrowth factor receptorImportant clinical prognostic markerTyrosine kinase growth factor receptorsSignal transduction moleculesFactor receptorCell cycle progressionIntracellular tyrosine kinaseSmall molecular inhibitorsTyrosine kinase domainNormal human cellsGrowth factorKinase domainTransduction moleculesCycle progressionEGFR expression correlatesTyrosine kinaseEGFR moleculesHuman cellsMetastatic phenotypeConformational changesPrevents activationMolecular inhibitorsImportant therapeutic targetCetuximab: an epidermal growth factor receptor chemeric human-murine monoclonal antibody.
Harding J, Burtness B. Cetuximab: an epidermal growth factor receptor chemeric human-murine monoclonal antibody. Drugs Of Today 2005, 41: 107-27. PMID: 15821783, DOI: 10.1358/dot.2005.41.2.882662.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntibody SpecificityAntineoplastic AgentsApoptosisArea Under CurveCell ProliferationCetuximabChemotherapy, AdjuvantClinical Trials as TopicDrug Resistance, NeoplasmErbB ReceptorsHalf-LifeHumansNeoplasmsNeovascularization, PathologicRadiation ToleranceConceptsEpidermal growth factor receptorImportant clinical prognostic markerHydrophobic transmembrane regionCell cycle progressionIntracellular tyrosine kinaseLigand-binding domainNormal human cellsProtein phosphorylationTransmembrane regionCytoplasmic regionGene transcriptionGrowth factor receptorEndogenous ligandCycle progressionExtracellular domainTyrosine kinaseOverall downregulationHuman cellsConformational changesNew anticancer therapiesHuman tumor cell linesErbB familyTumor cell linesVariety of cancersFactor receptor