2024
De-Escalated Therapy and Early Treatment of Recurrences in HPV-Associated Head and Neck Cancer: The Potential for Biomarkers to Revolutionize Personalized Therapy
Yarbrough W, Schrank T, Burtness B, Issaeva N. De-Escalated Therapy and Early Treatment of Recurrences in HPV-Associated Head and Neck Cancer: The Potential for Biomarkers to Revolutionize Personalized Therapy. Viruses 2024, 16: 536. PMID: 38675879, PMCID: PMC11053602, DOI: 10.3390/v16040536.Peer-Reviewed Original ResearchConceptsHPV+ HNSCCHPV-associated head and neck cancerHead and neck cancerHuman papillomavirus-associatedDe-escalation therapyDetect recurrent diseaseTreatment of recurrenceHPV-associated cancersHead and neckEarly treatment of recurrencePapillomavirus-associatedDevelopment of biomarkersResponsive tumorsRecurrent diseaseStandard therapyCompanion biomarkersHPV carcinogenesisHPV vaccinationNeck cancerPoor prognosisDecrease morbidityHNSCCEarly treatmentMolecular vulnerabilitiesPersonalized therapy
2021
Mu-opioid receptor activation promotes in vitro and in vivo tumor growth in head and neck squamous cell carcinoma
Gorur A, Patiño M, Takahashi H, Corrales G, Pickering CR, Gleber-Netto FO, Myers JN, Cata JP. Mu-opioid receptor activation promotes in vitro and in vivo tumor growth in head and neck squamous cell carcinoma. Life Sciences 2021, 278: 119541. PMID: 33930368, DOI: 10.1016/j.lfs.2021.119541.Peer-Reviewed Original ResearchConceptsMu-opioid receptorsMOR activationTumor growthSelective MOR agonist DAMGOMu-opioid receptor activationNeck squamous cell carcinomaSquamous cell carcinoma progressionNeck squamous cell carcinoma progressionMOR agonist DAMGOSquamous cell carcinomaTumorigenesis of HNSCCPotential therapeutic targetVivo tumor growthAgonist DAMGOCell carcinomaSaline 0.9MOR agonistsTherapeutic targetCarcinoma progressionReceptor activationHNSCCVivo studiesColony formationCell linesMe-Phe
2020
71P A phase II study of ADU-S100 in combination with pembrolizumab in adult patients with PD-L1+ recurrent or metastatic HNSCC: Preliminary safety, efficacy and PK/PD results
Zandberg D, Ferris R, Laux D, Mehra R, Nabell L, Kaczmar J, Gibson M, Kim Y, Neupane P, Bauman J, Julian R, Adkins D, Cohen E, Burtness B, Bermingham C, Dupage A, Desbien A, Loi A, Nuyten D, Saba N. 71P A phase II study of ADU-S100 in combination with pembrolizumab in adult patients with PD-L1+ recurrent or metastatic HNSCC: Preliminary safety, efficacy and PK/PD results. Annals Of Oncology 2020, 31: s1446-s1447. DOI: 10.1016/j.annonc.2020.10.559.Peer-Reviewed Original ResearchComparing programmed death ligand 1 scores for predicting pembrolizumab efficacy in head and neck cancer
Emancipator K, Huang L, Aurora-Garg D, Bal T, Cohen EEW, Harrington K, Soulières D, Le Tourneau C, Licitra L, Burtness B, Swaby R. Comparing programmed death ligand 1 scores for predicting pembrolizumab efficacy in head and neck cancer. Modern Pathology 2020, 34: 532-541. PMID: 33239737, DOI: 10.1038/s41379-020-00710-9.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalB7-H1 AntigenBiomarkers, TumorBiopsyClinical Decision-MakingClinical Trials, Phase III as TopicDecision Support TechniquesDisease ProgressionHead and Neck NeoplasmsHumansImmunohistochemistryPredictive Value of TestsProgression-Free SurvivalRandomized Controlled Trials as TopicRetrospective StudiesSquamous Cell Carcinoma of Head and NeckTime FactorsConceptsTumor proportion scoreObjective response ratePD-L1 expression statusDeath ligand 1 (PD-L1) expressionNeck squamous cell carcinomaImmune checkpoint inhibitorsLigand 1 expressionPD-L1 statusProgression-free survivalSquamous cell carcinomaKEYNOTE-040Pembrolizumab efficacyCheckpoint inhibitorsOverall survivalMetastatic HNSCCCell carcinomaNeck cancerClinical trialsProportion scoreInvestigator's choiceResponse rateExpression statusYouden indexHNSCCPatientsThe role of vitamin D in head and neck cancer
Izreig S, Hajek M, Edwards HA, Mehra S, Sasaki C, Judson BL, Rahmati RW. The role of vitamin D in head and neck cancer. Laryngoscope Investigative Otolaryngology 2020, 5: 1079-1088. PMID: 33364397, PMCID: PMC7752058, DOI: 10.1002/lio2.469.Peer-Reviewed Original ResearchVitamin DIntensive multi-modal therapyNeck squamous cell carcinomaManagement of HNSCCRise of immunotherapySet of malignanciesSquamous cell carcinomaMulti-modal therapyTreatment of HNSCCActive hormone calcitriolLimited data existsConsiderable morbiditySignificant morbiditySafe interventionCell carcinomaNeck cancerHormone calcitriolPatient outcomesEffective modalityHNSCCAdvanced stageMEDLINE databaseAvailable evidenceCalcium physiologyMorbidityPembrolizumab given concomitantly with chemoradiation and as maintenance therapy for locally advanced head and neck squamous cell carcinoma: KEYNOTE-412
Machiels JP, Tao Y, Burtness B, Tahara M, Licitra L, Rischin D, Waldron J, Simon C, Gregoire V, Harrington K, Alves GV, Lima I, Pointreau Y, Hughes B, Aksoy S, Hetnal M, Ge JY, Brown H, Cheng J, Bidadi B, Siu LL. Pembrolizumab given concomitantly with chemoradiation and as maintenance therapy for locally advanced head and neck squamous cell carcinoma: KEYNOTE-412. Future Oncology 2020, 16: 1235-1243. PMID: 32490686, DOI: 10.2217/fon-2020-0184.Peer-Reviewed Original ResearchConceptsNeck squamous cell carcinomaPhase III trialsSquamous cell carcinomaChemoradiation therapyAdvanced headIII trialsCell carcinomaImmune checkpoint inhibitor pembrolizumabLarge phase III trialsCheckpoint inhibitor pembrolizumabUse of pembrolizumabCurrent treatment guidelinesAdvanced HNSCCAdvanced diseaseMaintenance therapyMetastatic HNSCCTreatment guidelinesMaintenance treatmentMultimodal treatmentPembrolizumabPatientsAntitumor activityIB dataChemoradiationHNSCCSynthetic Lethal Targeting of Mitotic Checkpoints in HPV-Negative Head and Neck Cancer
Deneka AY, Einarson MB, Bennett J, Nikonova AS, Elmekawy M, Zhou Y, Lee JW, Burtness BA, Golemis EA. Synthetic Lethal Targeting of Mitotic Checkpoints in HPV-Negative Head and Neck Cancer. Cancers 2020, 12: 306. PMID: 32012873, PMCID: PMC7072436, DOI: 10.3390/cancers12020306.Peer-Reviewed Original ResearchG1/S checkpointNeck squamous cell carcinomaSingle-agent activitySquamous cell carcinomaHPV-negative headHPV-negative HNSCCHNSCC cell linesWEE1 inhibitor AZD1775S checkpointNegative HNSCCCell carcinomaHuman papillomavirusHNSCC cancerNeck cancerWorse outcomesSubset of drugsCommon mutational eventsDNA damageAnchorage-independent growthDual inhibitionClonogenic capacityClinical agentsSynthetic lethal targetingReduced activationHNSCCChapter 11 Trials and tribulations: Clinical trials and the future
Khanna S, Burtness B. Chapter 11 Trials and tribulations: Clinical trials and the future. 2020, 197-215. DOI: 10.1016/b978-0-12-820679-9.00011-6.Peer-Reviewed Original ResearchClinical trialsNeck cancerRecent landmark trialsRole of immunotherapyRisk stratification toolPromising clinical trialsMetastatic headPoor accrualSystemic treatmentLandmark trialsNeck specialistsStratification toolDedicated headTrialsCurrent standardCancerExciting advancesLack of fundingHeadImmunotherapyHPVHNSCCTherapyDiseasePathobiology
2019
Multi-Institutional Validation of Deep Learning for Pretreatment Identification of Extranodal Extension in Head and Neck Squamous Cell Carcinoma.
Kann BH, Hicks DF, Payabvash S, Mahajan A, Du J, Gupta V, Park HS, Yu JB, Yarbrough WG, Burtness BA, Husain ZA, Aneja S. Multi-Institutional Validation of Deep Learning for Pretreatment Identification of Extranodal Extension in Head and Neck Squamous Cell Carcinoma. Journal Of Clinical Oncology 2019, 38: 1304-1311. PMID: 31815574, DOI: 10.1200/jco.19.02031.Peer-Reviewed Original ResearchConceptsNeck squamous cell carcinomaExtranodal extensionSquamous cell carcinomaLymph nodesCell carcinomaContrast-enhanced CT scanDiagnostic abilityBoard-certified neuroradiologistsTreatment escalationCancer Genome AtlasPathologic confirmationPretreatment identificationDiagnostic challengeExternal validation data setsPathology resultsPretreatment imagingPoor prognosticatorClinical utilityCT scanPatientsClinical decisionHNSCCDiagnostic accuracyInstitutional ValidationGenome AtlasClinical Outcomes of Head and Neck Cancer Patients Who Undergo Resection, But Forgo Adjuvant Therapy
LOGANADANE G, KANN BH, PARK HS, JOHNSON SB, MEHRA S, JUDSON BL, BHATIA A, BELKACEMI Y, YARBROUGH WG, BURTNESS B, HUSAIN ZA. Clinical Outcomes of Head and Neck Cancer Patients Who Undergo Resection, But Forgo Adjuvant Therapy. Anticancer Research 2019, 39: 4885-4890. PMID: 31519591, DOI: 10.21873/anticanres.13674.Peer-Reviewed Original ResearchConceptsLocoregional recurrence-free survivalAdjuvant therapyNeck squamous cell carcinomaOutcomes of patientsRecurrence-free survivalSquamous cell carcinomaNeck cancer patientsHNSCC patientsClinical outcomesRecurrence rateCell carcinomaMean TTPCancer patientsPatientsTherapyResectionMonthsOutcomesHNSCCSurgeryCarcinomaHeadIncidenceProgressionThe changing therapeutic landscape of head and neck cancer
Cramer JD, Burtness B, Le QT, Ferris RL. The changing therapeutic landscape of head and neck cancer. Nature Reviews Clinical Oncology 2019, 16: 669-683. PMID: 31189965, DOI: 10.1038/s41571-019-0227-z.Peer-Reviewed Original ResearchConceptsNeck cancerTherapeutic landscapeNeck squamous cell carcinomaFirst immunotherapeutic agentHuman papillomavirus infectionNon-surgical therapyUpper aerodigestive tractSquamous cell carcinomaDifferent treatment modalitiesPapillomavirus infectionAerodigestive tractImmunotherapeutic agentsCell carcinomaTreatment modalitiesClinical trialsOral cavitySalivary glandsWidespread testingHNSCCDevelopment of strategiesCancerCurrent eraHeadOropharynxPatientsPDK1 Mediates NOTCH1-Mutated Head and Neck Squamous Carcinoma Vulnerability to Therapeutic PI3K/mTOR Inhibition
Sambandam V, Frederick MJ, Shen L, Tong P, Rao X, Peng S, Singh R, Mazumdar T, Huang C, Li Q, Pickering CR, Myers JN, Wang J, Johnson FM. PDK1 Mediates NOTCH1-Mutated Head and Neck Squamous Carcinoma Vulnerability to Therapeutic PI3K/mTOR Inhibition. Clinical Cancer Research 2019, 25: 3329-3340. PMID: 30770351, PMCID: PMC6548600, DOI: 10.1158/1078-0432.ccr-18-3276.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisCell Line, TumorCell ProliferationCRISPR-Cas SystemsDisease Models, AnimalDose-Response Relationship, DrugGene EditingGene ExpressionGene Knockdown TechniquesHumansLoss of Function MutationMicePhosphatidylinositol 3-KinasesProtein Kinase InhibitorsPyruvate Dehydrogenase Acetyl-Transferring KinaseReceptor, Notch1Signal TransductionSquamous Cell Carcinoma of Head and NeckTOR Serine-Threonine KinasesConceptsPI3K/mTOR inhibitorPI3K/mTOR inhibitionPI3K/mTOR pathway inhibitorsMTOR pathway inhibitorsHNSCC cell linesMTOR inhibitorsMTOR inhibitionCell linesPathway inhibitorNeck squamous cell carcinomaDrug-sensitive cell linesClinical response ratePI3K/mTOR pathwaySquamous cell carcinomaBiomarkers of responseOrthotopic xenograft modelCell carcinomaTumor sizeXenograft modelHNSCCSingle agentPDK1 overexpressionResponse rateMolecular vulnerabilitiesPharmacogenomic approach
2018
High tRNA Transferase NSUN2 Gene Expression is Associated with Poor Prognosis in Head and Neck Squamous Carcinoma
Lu L, Zhu G, Zeng H, Xu Q, Holzmann K. High tRNA Transferase NSUN2 Gene Expression is Associated with Poor Prognosis in Head and Neck Squamous Carcinoma. Cancer Investigation 2018, 36: 246-253. PMID: 29775108, DOI: 10.1080/07357907.2018.1466896.Peer-Reviewed Original ResearchConceptsPotential independent prognostic markerShorter overall survivalIndependent prognostic markerHigher mortality riskNeck squamous carcinomaPotential therapeutic targetRandom-effects modelOverall survivalSquamous carcinomaPoor prognosisPrognostic valuePrognostic markerMortality riskTherapeutic targetHNSCCNormal tissuesCell developmentExpressionGene expressionRNA methylationPatientsCarcinomaPrognosisNSUN2Important role
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 samplesDistinct pattern of TP53 mutations in human immunodeficiency virus–related head and neck squamous cell carcinoma
Gleber‐Netto F, Zhao M, Trivedi S, Wang J, Jasser S, McDowell C, Kadara H, Zhang J, Wang J, William WN, Lee JJ, Nguyen ML, Pai SI, Walline HM, Shin DM, Ferris RL, Carey TE, Myers JN, Pickering CR, Consortium F. Distinct pattern of TP53 mutations in human immunodeficiency virus–related head and neck squamous cell carcinoma. Cancer 2017, 124: 84-94. PMID: 29053175, PMCID: PMC5785080, DOI: 10.1002/cncr.31063.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedCadherinsCarcinoma, Squamous CellCase-Control StudiesCaspase 8Class I Phosphatidylinositol 3-KinasesCyclin D1Cyclin-Dependent Kinase Inhibitor p16Cyclin-Dependent Kinase Inhibitor p18ErbB ReceptorsF-Box-WD Repeat-Containing Protein 7FemaleHead and Neck NeoplasmsHistone MethyltransferasesHistone-Lysine N-MethyltransferaseHIV InfectionsHLA-A AntigensHumansIn Situ HybridizationIntracellular Signaling Peptides and ProteinsKelch-Like ECH-Associated Protein 1LIM Domain ProteinsMaleMiddle AgedNF-E2-Related Factor 2Nuclear ProteinsPapillomaviridaePapillomavirus InfectionsProtein Serine-Threonine KinasesProto-Oncogene Proteins p21(ras)Receptor, Notch1Receptor, Notch2Receptor, Transforming Growth Factor-beta Type IIReceptors, Transforming Growth Factor betaSquamous Cell Carcinoma of Head and NeckTranscription FactorsTumor Suppressor Protein p53Tumor Suppressor ProteinsConceptsHuman immunodeficiency virus-infected individualsHuman immunodeficiency virus (HIV) infectionNeck squamous cell carcinomaHuman papillomavirus (HPV) statusImmunodeficiency virus infectionVirus-infected individualsSquamous cell carcinomaSample of HIVTP53 mutation frequencyHNSCC patientsCell carcinomaHistopathological differencesPolymerase chain reactionIon Reporter softwareP16 immunostainingDistinct biologyVirus infectionHigh incidenceHIVHNSCCMultiplex polymerase chain reactionDistinct patternsHIV virusTumor samplesTP53 geneErbB activation signatures as potential biomarkers for anti-ErbB3 treatment in HNSCC
Alvarado D, Ligon GF, Lillquist JS, Seibel SB, Wallweber G, Neumeister VM, Rimm DL, McMahon G, LaVallee TM. ErbB activation signatures as potential biomarkers for anti-ErbB3 treatment in HNSCC. PLOS ONE 2017, 12: e0181356. PMID: 28723928, PMCID: PMC5517012, DOI: 10.1371/journal.pone.0181356.Peer-Reviewed Original ResearchConceptsNeuregulin-1NRG1 expressionErbB3 activationNeck squamous cell carcinomaSquamous cell carcinomaEnhanced anti-tumor activitySubset of HNSCCUnmet medical needHNSCC cell linesHNSCC patient samplesAnti-tumor activityGrowth factor αLigand neuregulin-1Cell carcinomaEGFR/ErbB familyHNSCC modelsCetuximab treatmentErbB receptor inhibitionReceptor inhibitionReceptor levelsRespective signaling pathwaysSolid tumorsTumor typesHNSCCPotential biomarkersPhenotypic heterogeneity of disseminated tumour cells is preset by primary tumour hypoxic microenvironments
Fluegen G, Avivar-Valderas A, Wang Y, Padgen MR, Williams JK, Nobre A, Calvo V, Cheung JF, Bravo-Cordero JJ, Entenberg D, Castracane J, Verkhusha V, Keely PJ, Condeelis J, Aguirre-Ghiso JA. Phenotypic heterogeneity of disseminated tumour cells is preset by primary tumour hypoxic microenvironments. Nature Cell Biology 2017, 19: 120-132. PMID: 28114271, PMCID: PMC5342902, DOI: 10.1038/ncb3465.Peer-Reviewed Original ResearchConceptsBreast cancer cellsDormant DTCsTumor hypoxic microenvironmentTumor cellsHypoxic microenvironmentCancer cellsDisseminated tumor cellsPrimary tumor microenvironmentDisease relapsePoor prognosisTarget organsP27 inductionTransgenic miceSolid tumorsTumor microenvironmentHypoxia genesHypoxiaPhenotypic heterogeneityMicroenvironmentCellsChemotherapyRelapseHNSCCPrognosisTherapy
2015
Down‐regulation of malic enzyme 1 and 2: Sensitizing head and neck squamous cell carcinoma cells to therapy‐induced senescence
Woo SH, Yang LP, Chuang HC, Fitzgerald A, Lee HY, Pickering C, Myers JN, Skinner HD. Down‐regulation of malic enzyme 1 and 2: Sensitizing head and neck squamous cell carcinoma cells to therapy‐induced senescence. Head & Neck 2015, 38: e934-e940. PMID: 25994759, DOI: 10.1002/hed.24129.Peer-Reviewed Original ResearchMeSH KeywordsCarcinoma, Squamous CellCell Line, TumorCellular SenescenceCyclin-Dependent Kinase Inhibitor p21Down-RegulationGene Expression Regulation, NeoplasticGene Knockdown TechniquesHead and Neck NeoplasmsHumansMalate DehydrogenaseMetforminRadiation, IonizingReactive Oxygen SpeciesTumor Suppressor Protein p53ConceptsTherapy-induced senescenceOverall survivalReactive oxygen speciesNeck squamous cell carcinomaSquamous cell carcinomaPoor overall survivalPotential therapeutic benefitHNSCC cell linesAntioxidant N-acetyl cysteineN-acetyl cysteinePoor outcomeCell carcinomaPatient outcomesHNSCC cellsGeneration of ROSTherapeutic benefitME2 expressionInduction of senescenceHNSCCP53 statusHigh expressionEnzyme expressionCell linesOxygen speciesOutcomesDetection of somatic mutations and HPV in the saliva and plasma of patients with head and neck squamous cell carcinomas
Wang Y, Springer S, Mulvey CL, Silliman N, Schaefer J, Sausen M, James N, Rettig EM, Guo T, Pickering CR, Bishop JA, Chung CH, Califano JA, Eisele DW, Fakhry C, Gourin CG, Ha PK, Kang H, Kiess A, Koch WM, Myers JN, Quon H, Richmon JD, Sidransky D, Tufano RP, Westra WH, Bettegowda C, Diaz LA, Papadopoulos N, Kinzler KW, Vogelstein B, Agrawal N. Detection of somatic mutations and HPV in the saliva and plasma of patients with head and neck squamous cell carcinomas. Science Translational Medicine 2015, 7: 293ra104. PMID: 26109104, PMCID: PMC4587492, DOI: 10.1126/scitranslmed.aaa8507.Peer-Reviewed Original ResearchConceptsNeck squamous cell carcinomaOral cavity cancerSquamous cell carcinomaTumor DNACell carcinomaOral cavityDetection of HNSCCLate-stage diseaseFraction of patientsPlasma of patientsTumor-specific DNASomatic mutationsHNSCC patientsPatientsValuable biomarkerClinical diagnosisHuman papillomavirus genesCancerSalivaCarcinomaRecurrenceBiomarkersHPVOropharynxHNSCCEvolutionary Action Score of TP53 Coding Variants Is Predictive of Platinum Response in Head and Neck Cancer Patients
Osman AA, Neskey DM, Katsonis P, Patel AA, Ward AM, Hsu TK, Hicks SC, McDonald TO, Ow TJ, Alves MO, Pickering CR, Skinner HD, Zhao M, Sturgis EM, Kies MS, El-Naggar A, Perrone F, Licitra L, Bossi P, Kimmel M, Frederick MJ, Lichtarge O, Myers JN. Evolutionary Action Score of TP53 Coding Variants Is Predictive of Platinum Response in Head and Neck Cancer Patients. Cancer Research 2015, 75: 1205-1215. PMID: 25691460, PMCID: PMC4615655, DOI: 10.1158/0008-5472.can-14-2729.Peer-Reviewed Original ResearchConceptsNeck cancer patientsEvolutionary action scoreCancer patientsTP53 mutationsNeck squamous cell carcinomaSquamous cell carcinomaCisplatin-based therapyPlatinum-based therapySubset of headThird of casesNovel scoring systemSurvival benefitProspective evaluationCell carcinomaPlatinum responsePreclinical modelsTreatment selectionAction scoresScoring systemPatientsHNSCCTherapyCoding variantPredictive responseScores
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