2021
STING enhances cell death through regulation of reactive oxygen species and DNA damage
Hayman TJ, Baro M, MacNeil T, Phoomak C, Aung TN, Cui W, Leach K, Iyer R, Challa S, Sandoval-Schaefer T, Burtness BA, Rimm DL, Contessa JN. STING enhances cell death through regulation of reactive oxygen species and DNA damage. Nature Communications 2021, 12: 2327. PMID: 33875663, PMCID: PMC8055995, DOI: 10.1038/s41467-021-22572-8.Peer-Reviewed Original Research
2019
Neuregulin Signaling Is a Mechanism of Therapeutic Resistance in Head and Neck Squamous Cell Carcinoma
Baro M, Lopez Sambrooks C, Burtness BA, Lemmon MA, Contessa JN. Neuregulin Signaling Is a Mechanism of Therapeutic Resistance in Head and Neck Squamous Cell Carcinoma. Molecular Cancer Therapeutics 2019, 18: 2124-2134. PMID: 31387891, PMCID: PMC6825559, DOI: 10.1158/1535-7163.mct-19-0163.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, MonoclonalCell Line, TumorCell ProliferationCell SurvivalCetuximabDrug Resistance, NeoplasmFemaleHead and Neck NeoplasmsHumansMiceNeuregulinsProto-Oncogene Proteins c-aktReceptor, ErbB-3Signal TransductionSquamous Cell Carcinoma of Head and NeckUp-RegulationXenograft Model Antitumor AssaysConceptsNeck squamous cell carcinomaSquamous cell carcinomaTherapeutic resistanceCell carcinomaResistant cellsConcentrations of cetuximabEFM-19 cellsCetuximab-resistant cellsActionable therapeutic targetsHNSCC cell linesTumor growth experimentsInhibition of EGFRErbB3 antibodyNeuregulin expressionOverall survivalTreatment regimensCetuximab resistanceTherapeutic targetAutocrine loopLocal controlTumor growthRadiotherapyEGFR inhibitionCetuximabNeuregulin SignalingCombined Aurora Kinase A (AURKA) and WEE1 Inhibition Demonstrates Synergistic Antitumor Effect in Squamous Cell Carcinoma of the Head and Neck
Lee JW, Parameswaran J, Sandoval-Schaefer T, Eoh KJ, Yang DH, Zhu F, Mehra R, Sharma R, Gaffney SG, Perry EB, Townsend JP, Serebriiskii IG, Golemis EA, Issaeva N, Yarbrough WG, Koo JS, Burtness B. Combined Aurora Kinase A (AURKA) and WEE1 Inhibition Demonstrates Synergistic Antitumor Effect in Squamous Cell Carcinoma of the Head and Neck. Clinical Cancer Research 2019, 25: 3430-3442. PMID: 30755439, PMCID: PMC6548643, DOI: 10.1158/1078-0432.ccr-18-0440.Peer-Reviewed Original ResearchAnimalsAntineoplastic AgentsApoptosisAurora Kinase ACell Cycle ProteinsCell Line, TumorDisease Models, AnimalDrug SynergismFemaleFluorescent Antibody TechniqueGene ExpressionHumansMaleMiceNeoplasm GradingNeoplasm StagingProtein Kinase InhibitorsProtein-Tyrosine KinasesSquamous Cell Carcinoma of Head and NeckXenograft Model Antitumor Assays
2017
Demethylation Therapy as a Targeted Treatment for Human Papillomavirus–Associated Head and Neck Cancer
Biktasova A, Hajek M, Sewell A, Gary C, Bellinger G, Deshpande HA, Bhatia A, Burtness B, Judson B, Mehra S, Yarbrough WG, Issaeva N. Demethylation Therapy as a Targeted Treatment for Human Papillomavirus–Associated Head and Neck Cancer. Clinical Cancer Research 2017, 23: 7276-7287. PMID: 28916527, DOI: 10.1158/1078-0432.ccr-17-1438.Peer-Reviewed Original ResearchConceptsClinical trialsHNSCC cellsMatrix metalloproteinasesHuman papillomavirus-associated headNeck squamous cell carcinomaSquamous cell carcinomaAbility of HPVClin Cancer ResTumor cell proliferationNeck cancer cellsWindow trialsCell carcinomaEffective therapyPreclinical modelsHPVHPV oncogenesMouse modelMouse blood vesselsDNA demethylating agentHNSCCXenografted tumorsHPV genesIFN responseTherapyTumor samples
2013
Novel targets in HPV-negative head and neck cancer: overcoming resistance to EGFR inhibition
Burtness B, Bauman JE, Galloway T. Novel targets in HPV-negative head and neck cancer: overcoming resistance to EGFR inhibition. The Lancet Oncology 2013, 14: e302-e309. PMID: 23816296, DOI: 10.1016/s1470-2045(13)70085-8.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, Monoclonal, HumanizedAntineoplastic AgentsCetuximabDrug DesignDrug Resistance, NeoplasmErbB ReceptorsHead and Neck NeoplasmsHistone Deacetylase InhibitorsHumansMolecular Targeted TherapyPapillomaviridaeProtein Kinase InhibitorsProto-Oncogene Proteins c-metReceptor, ErbB-2Signal TransductionTreatment OutcomeConceptsHPV-negative headNeck cancerHuman papillomavirusEGFR inhibitionSingle-agent cetuximabLow cure rateMonoclonal antibody cetuximabActive therapyCytotoxic chemotherapyDisease survivalCure rateMechanisms of resistanceAntibody cetuximabResponse rateCetuximabEGFRNovel targetReceptor tyrosine kinasesCancerTherapyHistone deacetylaseChemotherapyHabitual exposureModest effectNuclear functionsTargeting C4-Demethylating Genes in the Cholesterol Pathway Sensitizes Cancer Cells to EGF Receptor Inhibitors via Increased EGF Receptor Degradation
Sukhanova A, Gorin A, Serebriiskii IG, Gabitova L, Zheng H, Restifo D, Egleston BL, Cunningham D, Bagnyukova T, Liu H, Nikonova A, Adams GP, Zhou Y, Yang DH, Mehra R, Burtness B, Cai KQ, Klein-Szanto A, Kratz LE, Kelley RI, Weiner LM, Herman GE, Golemis EA, Astsaturov I. Targeting C4-Demethylating Genes in the Cholesterol Pathway Sensitizes Cancer Cells to EGF Receptor Inhibitors via Increased EGF Receptor Degradation. Cancer Discovery 2013, 3: 96-111. PMID: 23125191, PMCID: PMC3546138, DOI: 10.1158/2159-8290.cd-12-0031.Peer-Reviewed Original ResearchConceptsEGF receptorPathway genesDegradation of EGFROncogenic EGF receptorEGF receptor degradationBiosynthesis pathway genesPlatelet-derived growth factor receptorEndocytic traffickingVesicular traffickingEGF receptor inhibitorEGFR degradationDimerization partnerBioinformatics modelingGrowth factor receptorUnexpected roleReceptor degradationCancer cell viabilityNSDHLSC4MOLCholesterol pathwayGenesFactor receptorCancer resistanceEGFR antagonistsCancer cells
2007
Her 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
2006
Novel targets in pancreatic cancer: focus on future paths to therapy
Cohen SJ, Burtness BA. Novel targets in pancreatic cancer: focus on future paths to therapy. Expert Opinion On Therapeutic Targets 2006, 10: 771-775. PMID: 16981833, DOI: 10.1517/14728222.10.5.771.Peer-Reviewed Original ResearchConceptsPancreatic cancerNew therapeuticsRational clinical trialsTobacco-related malignanciesDismal overall survivalPancreatic cancer pathogenesisPreclinical model systemsAdvanced diseaseOverall survivalCytotoxic therapyHER2 inhibitionClinical trialsTherapeutic increasesClinical dataClinical testingTissue factorNew casesCancer pathogenesisNovel targetCancerNew targetsTherapyEqual numberTherapeuticsMalignancyAntibody therapy for early-stage breast cancer: trastuzumab adjuvant and neoadjuvant trials
Mehra R, Burtness B. Antibody therapy for early-stage breast cancer: trastuzumab adjuvant and neoadjuvant trials. Expert Opinion On Biological Therapy 2006, 6: 951-962. PMID: 16918262, DOI: 10.1517/14712598.6.9.951.Peer-Reviewed Original ResearchConceptsBreast cancerVascular endothelial growth factor levelsEarly-stage breast cancerYear of trastuzumabHER2/neu geneGrowth factor levelsBreast cancer cellsAdjuvant settingNeoadjuvant trialsOverall survivalRandomised trialsAggressive courseImproved outcomesImmune responseTrastuzumabActivation initiatesFactor levelsHER2 phosphorylationMonoclonal antibodiesNeu geneCancerCancer cellsHER2TrialsAntibodies
2005
Cetuximab: 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
2004
A preclinical xenotransplantation animal model to assess human hematopoietic stem cell engraftment
Angelopoulou MK, Rinder H, Wang C, Burtness B, Cooper DL, Krause DS. A preclinical xenotransplantation animal model to assess human hematopoietic stem cell engraftment. Transfusion 2004, 44: 555-566. PMID: 15043572, DOI: 10.1111/j.1537-2995.2004.03285.x.Peer-Reviewed Original ResearchConceptsHuman cell engraftmentHuman CFU-MKCell engraftmentPLT engraftmentWBC engraftmentCFU-MKAutologous PBPC transplantationEnhancement of engraftmentMultilineage human hematopoiesisPercent of patientsPLT recoveryHuman WBCsMouse xenotransplantation modelHematopoietic stem cell engraftmentHuman hematopoietic stem cell engraftmentNOD-SCID miceStem cell engraftmentXenogeneic transplant modelBlood weeklyPBPC transplantationTransplant modelLiver abnormalitiesPatients CorrelateAutologous transplantationHuman PLTs
1998
Cytosine Deaminase Adenoviral Vector and 5-Fluorocytosine Selectively Reduce Breast Cancer Cells 1 Million-Fold When They Contaminate Hematopoietic Cells: A Potential Purging Method for Autologous Transplantation
Garcia-Sanchez F, Pizzorno G, Fu SQ, Nanakorn T, Krause DS, Liang J, Adams E, Leffert JJ, Yin LH, Cooperberg MR, Hanania E, Wang WL, Won JH, Peng XY, Cote R, Brown R, Burtness B, Giles R, Crystal R, Deisseroth AB. Cytosine Deaminase Adenoviral Vector and 5-Fluorocytosine Selectively Reduce Breast Cancer Cells 1 Million-Fold When They Contaminate Hematopoietic Cells: A Potential Purging Method for Autologous Transplantation. Blood 1998, 92: 672-682. PMID: 9657770, DOI: 10.1182/blood.v92.2.672.Peer-Reviewed Original ResearchMeSH KeywordsAdenoviridaeAnimalsAntimetabolites, AntineoplasticBreast NeoplasmsCell DeathCytosine DeaminaseFemaleFlucytosineFluorouracilGene Transfer TechniquesGenetic VectorsHematopoietic Stem Cell MobilizationHematopoietic Stem Cell TransplantationHematopoietic Stem CellsHumansMaleMiceNucleoside DeaminasesProdrugsTransplantation, AutologousTumor Cells, CulturedConceptsBreast cancer cellsPeripheral blood mononuclear cellsBreast cancer patientsCancer patientsCytosine deaminase geneHuman mammary epithelial cellsAdenoviral vectorCancer cellsHours of exposureHematopoietic cellsAutologous stem cell productsMarrow cellsEscherichia coli cytosine deaminase geneReplication-incompetent adenoviral vectorEpithelial cellsChemotherapy-induced myelosuppressionBreast cancer cell line MCF-7Blood mononuclear cellsEarly hematopoietic precursor cellsMale donor miceCancer cell line MCF-7Fluorescence-activated cell sorting (FACS) analysisMCF-7 breast cancer cellsNormal human mammary epithelial cellsMDA-MB-453Phase I clinical and pharmacological studies of benzylacyclouridine, a uridine phosphorylase inhibitor.
Pizzorno G, Yee L, Burtness BA, Marsh JC, Darnowski JW, Chu MY, Chu SH, Chu E, Leffert JJ, Handschumacher RE, Calabresi P. Phase I clinical and pharmacological studies of benzylacyclouridine, a uridine phosphorylase inhibitor. Clinical Cancer Research 1998, 4: 1165-75. PMID: 9607574.Peer-Reviewed Original ResearchConceptsPreclinical studiesDose levelsUridine concentrationPhase I clinical trialGrade 1 constipationGrade 1 elevationGrade 1 fatigueGrade 1 feverGrade 2 anemiaOral dose levelsSingle oral doseTreatment of patientsPlasma uridine concentrationBiochemical end pointsFirst-order clearanceAverage peak concentrationCancer cell linesAdvanced cancerOral dosePlasma levelsPlasma uridineClinical trialsPlasma concentrationsSustained elevationTracer dose