2024
Th2 Cells Are Associated with Tumor Recurrence Following Radiation
Abdelhakiem M, Bao R, Pifer P, Molkentine D, Molkentine J, Hefner A, Beadle B, Heymach J, Luke J, Ferris R, Pickering C, Wang J, Patel R, Skinner H. Th2 Cells Are Associated with Tumor Recurrence Following Radiation. Cancers 2024, 16: 1586. PMID: 38672668, PMCID: PMC11049347, DOI: 10.3390/cancers16081586.Peer-Reviewed Original ResearchHead and neck squamous cell carcinomaLocoregional recurrenceValidation cohortTh2 infiltrationDiscovery cohortTh2 cellsTreatment of multiple solid tumorsAssociated with locoregional recurrenceNeck squamous cell carcinomaAssociated with tumor recurrencePrognostic immune biomarkersAntitumor immune responseTumor immune infiltrationSquamous cell carcinomaMultiple solid tumorsIndependent validation cohortResponse to radiationImmune cell typesMechanism of radiation resistanceAssociated with outcomeAdjuvant radiationTumor recurrenceHNSCC tumorsCell carcinomaImmune infiltration
2023
FAK drives resistance to therapy in HPV-negative head and neck cancer in a p53-dependent manner.
Pifer P, Yang L, Kumar M, Xie T, Frederick M, Hefner A, Beadle B, Molkentine D, Molkentine J, Dhawan A, Abdelhakiem M, Osman A, Leibowitz B, Myers J, Pickering C, Sandulache V, Heymach J, Skinner H. FAK drives resistance to therapy in HPV-negative head and neck cancer in a p53-dependent manner. Clinical Cancer Research 2023, 30: 187-197. PMID: 37819945, PMCID: PMC10767302, DOI: 10.1158/1078-0432.ccr-23-0964.Peer-Reviewed Original ResearchConceptsHPV-negative headHPV-negative HNSCC tumorsWorse disease-free survivalNeck squamous cell carcinomaMutant TP53HPV-negative HNSCC cell linesBackbone of therapyDisease-free survivalPlatinum-based chemotherapySquamous cell carcinomaHPV-negative HNSCCHNSCC cell linesCell linesWild-type TP53Cisplatin-resistant cell linesCell carcinomaHNSCC cohortNeck cancerHNSCC tumorsVivo shRNA screenWorse outcomesA Deep Learning Onion Peeling Approach to Measure Oral Epithelium Layer Number
Zhang X, Gleber-Netto F, Wang S, Jin K, Yang D, Gillenwater A, Myers J, Ferrarotto R, Pickering C, Xiao G. A Deep Learning Onion Peeling Approach to Measure Oral Epithelium Layer Number. Cancers 2023, 15: 3891. PMID: 37568707, PMCID: PMC10416878, DOI: 10.3390/cancers15153891.Peer-Reviewed Original ResearchOral epitheliumNeck squamous cell carcinomaSquamous cell carcinomaPatients' qualityCell carcinomaDysplasia severityEarly diagnosisPathologist's examinationOral cavityComplex cancersClinical relevanceDysplasia diagnosisSurvival analysisEpithelium layerDiagnostic potentialCell layerIntra-observer variationDiagnosisEpitheliumClose correlationPotential additionPrognosisCarcinomaCancerHRAS Mutations Define a Distinct Subgroup in Head and Neck Squamous Cell Carcinoma
Coleman N, Marcelo K, Hopkins J, Khan N, Du R, Hong L, Park E, Balsara B, Leoni M, Pickering C, Myers J, Heymach J, Albacker L, Hong D, Gillison M, Le X. HRAS Mutations Define a Distinct Subgroup in Head and Neck Squamous Cell Carcinoma. JCO Precision Oncology 2023, 7: e2200211. PMID: 36603172, PMCID: PMC9928766, DOI: 10.1200/po.22.00211.Peer-Reviewed Original ResearchConceptsNeck squamous cell carcinomaMD Anderson Cancer CenterSquamous cell carcinomaAnderson Cancer CenterCo-occurring mutationsClinical courseSurvival outcomesCancer CenterCell carcinomaShorter disease-free survivalPoor clinic outcomePrimary definitive treatmentTherapeutic combination strategiesDisease-free survivalPoor clinical outcomePatient demographic informationImproved OSDefinitive treatmentMedian ageOverall survivalFoundation MedicineMale patientsClinical outcomesClinic outcomesTreatment response
2022
Clinical Trial Development in TP53-Mutated Locally Advanced and Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma
Rodriguez CP, Kang H, Geiger JL, Burtness B, Chung CH, Pickering CR, Fakhry C, Le QT, Yom SS, Galloway TJ, Golemis E, Li A, Shoop J, Wong S, Mehra R, Skinner H, Saba NF, Flores ER, Myers JN, Ford JM, Karchin R, Ferris RL, Kunos C, Lynn JM, Malik S. Clinical Trial Development in TP53-Mutated Locally Advanced and Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma. Journal Of The National Cancer Institute 2022, 114: 1619-1627. PMID: 36053203, PMCID: PMC9745425, DOI: 10.1093/jnci/djac163.Peer-Reviewed Original ResearchConceptsNeck squamous cell carcinomaSquamous cell carcinomaClinical trialsCell carcinomaTrial designTP53 mutationsNational Clinical Trials NetworkMetastatic disease settingsClinical trial developmentClinical Trials NetworkNovel therapeutic approachesNational Cancer InstituteMetastatic headTP53-mutated tumorsWorse outcomesClinical studiesFrequent genetic eventTherapeutic approachesCancer InstituteTrial developmentBreakout groupsPatientsDisease settingsBiomarker integrationTrials NetworkHigh enhancer activity is an epigenetic feature of HPV negative atypical head and neck squamous cell carcinoma
Callahan SC, Kochat V, Liu Z, Raman AT, Divenko M, Schulz J, Terranova CJ, Ghosh AK, Tang M, Johnson FM, Wang J, Skinner HD, Pickering CR, Myers JN, Rai K. High enhancer activity is an epigenetic feature of HPV negative atypical head and neck squamous cell carcinoma. Frontiers In Cell And Developmental Biology 2022, 10: 936168. PMID: 35927986, PMCID: PMC9343809, DOI: 10.3389/fcell.2022.936168.Peer-Reviewed Original ResearchNeck squamous cell carcinomaSquamous cell carcinomaCell carcinomaCell linesHNSCC cell linesAtypical headResistance pathwaysHNSCC subtypesFrequent recurrenceMolecular subtypesHeterogeneous diseaseLipid metabolismSubtypesSignificant mortalityCarcinomaMAPK signalingFuture targetsHigh enhancer activityDiseaseAtypicalsBromodomain inhibitorsTCGA tumorsEnhancer activityBasalMesenchymalInduction Chemotherapy with or without Erlotinib in Patients with Head and Neck Squamous Cell Carcinoma Amenable for Surgical Resection
Le X, Gleber-Netto FO, Rubin ML, Qing Y, Du R, Kies M, Blumenschein G, Lu C, Johnson FM, Bell D, Lewis J, Zhang J, Feng L, Wilson K, Marcelo-Lewis K, Wang J, Ginsberg L, Gillison M, Lee JJ, Meric-Berstam F, Mills GB, William W, Myers JN, Pickering CR. Induction Chemotherapy with or without Erlotinib in Patients with Head and Neck Squamous Cell Carcinoma Amenable for Surgical Resection. Clinical Cancer Research 2022, 28: 2796-2806. PMID: 35443062, DOI: 10.1158/1078-0432.ccr-21-3239.Peer-Reviewed Original ResearchOral squamous cell carcinomaProgression-free survivalSquamous cell carcinomaSurgical resectionCell carcinomaTreatment-related adverse event ratesAdvanced oral squamous cell carcinomaMajor pathologic response rateNeck squamous cell carcinomaPathologic response ratePlatinum-taxane chemotherapyCycles of chemotherapyAdverse event ratesMajor pathological responseExcellent clinical outcomesAddition of erlotinibCycles of treatmentPre-treatment samplesConcurrent erlotinibErlotinib armNeoadjuvant erlotinibInduction chemotherapyNeoadjuvant chemotherapySecondary endpointsDefinitive surgery
2021
Low doses of methylnaltrexone inhibits head and neck squamous cell carcinoma growth in vitro and in vivo by acting on the mu‐opioid receptor
Gorur A, Patiño M, Shi T, Corrales G, Takahashi H, Rangel R, Gleber‐Netto F, Pickering C, Myers JN, Cata JP. Low doses of methylnaltrexone inhibits head and neck squamous cell carcinoma growth in vitro and in vivo by acting on the mu‐opioid receptor. Journal Of Cellular Physiology 2021, 236: 7698-7710. PMID: 34038587, DOI: 10.1002/jcp.30421.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsCell Line, TumorCell MovementCell ProliferationEpithelial-Mesenchymal TransitionHead and Neck NeoplasmsHumansMaleMice, Inbred C57BLMice, NudeNaltrexoneNarcotic AntagonistsNeoplasm InvasivenessQuaternary Ammonium CompoundsReceptors, Opioid, muSignal TransductionSquamous Cell Carcinoma of Head and NeckTumor BurdenXenograft Model Antitumor AssaysConceptsMu-opioid receptorsEffects of methylnaltrexoneHNSCC cell linesTumor growthCell linesNeck squamous cell carcinoma growthNeck squamous cell carcinomaDifferent HNSCC cell linesClonogenic activitySquamous cell carcinoma growthSquamous cell carcinomaLung cancer cell linesCyclic adenosine monophosphate levelsTumor-bearing miceAggressive cell behaviorEpithelial-mesenchymal transitionAdenosine monophosphate levelsCancer cell linesCell carcinomaMethylnaltrexoneCarcinoma growthTherapeutic targetLow dosesFaDu cellsMetastasis formationMu-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-PheTargeting resistance to radiation-immunotherapy in cold HNSCCs by modulating the Treg-dendritic cell axis
Knitz MW, Bickett TE, Darragh LB, Oweida AJ, Bhatia S, Van Court B, Bhuvane S, Piper M, Gadwa J, Mueller AC, Nguyen D, Nangia V, Osborne DG, Bai X, Ferrara SE, Boss MK, Goodspeed A, Burchill MA, Tamburini BAJ, Chan ED, Pickering CR, Clambey ET, Karam SD. Targeting resistance to radiation-immunotherapy in cold HNSCCs by modulating the Treg-dendritic cell axis. Journal For ImmunoTherapy Of Cancer 2021, 9: e001955. PMID: 33883256, PMCID: PMC8061827, DOI: 10.1136/jitc-2020-001955.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic Agents, ImmunologicalBasic-Leucine Zipper Transcription FactorsCell Line, TumorCombined Modality TherapyDendritic CellsDrug Resistance, NeoplasmHead and Neck NeoplasmsImmune Checkpoint InhibitorsImmunotherapyInterleukin-2 Receptor alpha SubunitLymphocyte DepletionMice, Inbred BALB CMice, Inbred C57BLMice, KnockoutPhenotypeRadiation Dose HypofractionationRadiation ToleranceRepressor ProteinsSquamous Cell Carcinoma of Head and NeckT-Lymphocytes, RegulatoryTumor BurdenTumor MicroenvironmentTumor Necrosis Factor Receptor Superfamily, Member 9ConceptsCombination radiation therapyRadiation therapyDendritic cellsLymph nodesMouse modelRadioresistant tumorsRegulatory T-cell depletionT cell effector responsesTumor-draining lymph nodesNeck squamous cell carcinomaOral squamous cell carcinoma tumorsT cell-dependent responsesSquamous cell carcinoma tumorsAnti-CD137 treatmentDC activation statusGy x 5Higher Treg numbersPlasticity of TregsAdoptive transfer studiesT-cell depletionSquamous cell carcinomaCell-dependent responsesOrthotopic mouse modelTumor necrosis factorαNew therapeutic opportunitiesWhole-exome Sequencing in Penile Squamous Cell Carcinoma Uncovers Novel Prognostic Categorization and Drug Targets Similar to Head and Neck Squamous Cell CarcinomaClinical Implications of WES in Penile Squamous Carcinoma
Chahoud J, Gleber-Netto FO, McCormick BZ, Rao P, Lu X, Guo M, Morgan MB, Chu RA, Martinez-Ferrer M, Eterovic AK, Pickering CR, Pettaway CA. Whole-exome Sequencing in Penile Squamous Cell Carcinoma Uncovers Novel Prognostic Categorization and Drug Targets Similar to Head and Neck Squamous Cell CarcinomaClinical Implications of WES in Penile Squamous Carcinoma. Clinical Cancer Research 2021, 27: 2560-2570. PMID: 33441293, DOI: 10.1158/1078-0432.ccr-20-4004.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overBiomarkers, TumorCase-Control StudiesComputational BiologyDisease ManagementDisease SusceptibilityExome SequencingHumansMaleMiddle AgedMolecular Targeted TherapyMutationNeoplasm GradingNeoplasm StagingPenile NeoplasmsPrognosisSquamous Cell Carcinoma of Head and NeckConceptsPenile squamous cell carcinomaSquamous cell carcinomaCell carcinomaHuman papilloma virus testingNeck squamous cell carcinomaNotch pathway alterationsMutation signaturesTumor mutation burdenWorse overall survivalLimited treatment optionsWhole-exome sequencing analysisPenile squamous carcinomaPotential clinical implicationsMutational signaturesDefective DNA mismatch repairCancer Genome Atlas studyWhole-exome sequencingNovel druggable targetsDistinct mutational signaturesNormal penile tissuesOverall survivalWorse survivalHigh TMBSquamous carcinomaPenile tissue
2020
Caspase 8 loss radiosensitizes head and neck squamous cell carcinoma to SMAC mimetic induced necroptosis
Uzunparmak B, Gao M, Lindemann A, Erikson K, Wang L, Lin E, Frank SJ, Gleber-Netto FO, Zhao M, Skinner HD, Newton JM, Sikora AG, Myers JN, Pickering CR. Caspase 8 loss radiosensitizes head and neck squamous cell carcinoma to SMAC mimetic induced necroptosis. JCI Insight 2020, 5: e139837. PMID: 33108350, PMCID: PMC7714407, DOI: 10.1172/jci.insight.139837.Peer-Reviewed Original ResearchConceptsReceptor-interacting serine/threonine-protein kinase 3Caspase-8Serine/threonine-protein kinase 3Regulated cell death mechanismsPan-caspase inhibitor z-VADSecond mitochondria-derived activatorProtein kinase 3Cell death mechanismsRIP3 functionSmac mimeticsZ-VADKinase 3Death mechanismsMolecular underpinningsNecroptosis pathwayHNSCC cell linesNecroptosisRIP3 expressionCancer cellsCell linesBirinapantNeck squamous cell carcinomaCASP8 mutationsSquamous cell carcinomaSyngeneic mouse modelIdentifying predictors of HPV‐related head and neck squamous cell carcinoma progression and survival through patient‐derived models
Facompre ND, Rajagopalan P, Sahu V, Pearson AT, Montone KT, James CD, Gleber‐Netto F, Weinstein GS, Jalaly J, Lin A, Rustgi AK, Nakagawa H, Califano JA, Pickering CR, White EA, Windle BE, Morgan IM, Cohen RB, Gimotty PA, Basu D. Identifying predictors of HPV‐related head and neck squamous cell carcinoma progression and survival through patient‐derived models. International Journal Of Cancer 2020, 147: 3236-3249. PMID: 32478869, PMCID: PMC7554059, DOI: 10.1002/ijc.33125.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsClass I Phosphatidylinositol 3-KinasesErbB ReceptorsExome SequencingFemaleGenetic Association StudiesHead and Neck NeoplasmsHumansMaleMiceMutationNeoplasm TransplantationPapillomaviridaePapillomavirus E7 ProteinsPapillomavirus InfectionsPatient-Specific ModelingPrognosisSquamous Cell Carcinoma of Head and NeckSurvival AnalysisTNF Receptor-Associated Factor 3ConceptsPatient-derived xenograftsTumor mutational burdenPreclinical modelsMutational burdenHuman papilloma virus-related headHigh tumor mutational burdenNeck squamous cell carcinomaSquamous cell carcinoma progressionNeck squamous cell carcinoma progressionInadequate preclinical modelsSquamous cell carcinomaDisease recurrence riskPatient-derived modelsLow engraftment rateWhole-exome sequencingViral oncogene functionPrognostic alterationsLocal progressionHPV- patientsCancer Genome AtlasCell carcinomaHPV casesPIK3CA mutationsEngraftment rateLethal outcome
2019
PDK1 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 approachDisruption of TP63-miR-27a* Feedback Loop by Mutant TP53 in Head and Neck Cancer
Chari NS, Ivan C, Le X, Li J, Mijiti A, Patel AA, Osman AA, Peterson CB, Williams MD, Pickering CR, Caulin C, Myers JN, Calin GA, Lai SY. Disruption of TP63-miR-27a* Feedback Loop by Mutant TP53 in Head and Neck Cancer. Journal Of The National Cancer Institute 2019, 112: 266-277. PMID: 31124563, PMCID: PMC7073912, DOI: 10.1093/jnci/djz097.Peer-Reviewed Original ResearchMeSH KeywordsCase-Control StudiesChromatin ImmunoprecipitationFeedback, PhysiologicalHead and Neck NeoplasmsHumansMicroRNAsMouth NeoplasmsMutationNeoplasm StagingPromoter Regions, GeneticSquamous Cell Carcinoma of Head and NeckSurvival RateTranscription FactorsTranscription, GeneticTumor Suppressor Protein p53Tumor Suppressor ProteinsConceptsMutant TP53Neck squamous cell carcinomaSquamous cell carcinomaHNSCC cell linesInhibits tumor growthEpidermal growth factor receptorFrequent eventRole of TP53PI3K pathwayGrowth factor receptorCancer Genome AtlasCell carcinomaNeck cancerHNSCC samplesPoor survivalEpidermal growth factorTumor growthVivo findingsTumor progressionPatient samplesTumor samplesTumor survivalTumor cellsNormal tissuesNovel targetPredicting Outcome in Head and Neck Cancer: miRNAs with Potentially Big Effects
Clump DA, Pickering CR, Skinner HD. Predicting Outcome in Head and Neck Cancer: miRNAs with Potentially Big Effects. Clinical Cancer Research 2019, 25: 1441-1442. PMID: 30413524, PMCID: PMC6415532, DOI: 10.1158/1078-0432.ccr-18-3078.Peer-Reviewed Original ResearchConceptsHigh-risk patient populationNeck squamous cell carcinomaFive-miRNA signatureSquamous cell carcinomaNovel miRNA signatureCell carcinomaClinical variablesHuman papillomavirusInferior outcomesPatient populationNeck cancerTreatment strategiesPredicting OutcomeMiRNA signatureNegative headOutcomesPatientsCarcinomaPapillomavirusCancerHeadWeekly paclitaxel, carboplatin, cetuximab, and cetuximab, docetaxel, cisplatin, and fluorouracil, followed by local therapy in previously untreated, locally advanced head and neck squamous cell carcinoma
Haddad RI, Massarelli E, Lee JJ, Lin HY, Hutcheson K, Lewis J, Garden AS, Blumenschein GR, William WN, Pharaon RR, Tishler RB, Glisson BS, Pickering C, Gold KA, Johnson FM, Rabinowits G, Ginsberg LE, Williams MD, Myers J, Kies MS, Papadimitrakopoulou V. Weekly paclitaxel, carboplatin, cetuximab, and cetuximab, docetaxel, cisplatin, and fluorouracil, followed by local therapy in previously untreated, locally advanced head and neck squamous cell carcinoma. Annals Of Oncology 2019, 30: 471-477. PMID: 30596812, PMCID: PMC7360148, DOI: 10.1093/annonc/mdy549.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Combined Chemotherapy ProtocolsCarboplatinCetuximabCisplatinDocetaxelFemaleFluorouracilHumansInduction ChemotherapyMaleMiddle AgedNeoplasm Recurrence, LocalNeoplasm StagingPaclitaxelPapillomaviridaePapillomavirus InfectionsProgression-Free SurvivalSquamous Cell Carcinoma of Head and NeckConceptsProgression-free survivalSquamous cell carcinomaHigh-risk groupNeck squamous cell carcinomaPrimary end pointInduction chemotherapyLocal therapyCell carcinomaC-TPFAdvanced headT stageHistorical controlsEnd pointPhase II clinical trialHuman papillomavirus (HPV) statusLow-risk groupEligible patientsMedian followWeekly paclitaxelLocoregional treatmentT3-4P16 statusClinical trialsRisk groupsHPV
2018
Comprehensive pharmacogenomic profiling of human papillomavirus-positive and -negative squamous cell carcinoma identifies sensitivity to aurora kinase inhibition in KMT2D mutants
Kalu NN, Mazumdar T, Peng S, Tong P, Shen L, Wang J, Banerjee U, Myers JN, Pickering CR, Brunell D, Stephan CC, Johnson FM. Comprehensive pharmacogenomic profiling of human papillomavirus-positive and -negative squamous cell carcinoma identifies sensitivity to aurora kinase inhibition in KMT2D mutants. Cancer Letters 2018, 431: 64-72. PMID: 29807113, DOI: 10.1016/j.canlet.2018.05.029.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisArea Under CurveAurora Kinase ABenzamidesBiomarkersCarcinoma, Squamous CellCell CycleCell LineCell ProliferationDNA-Binding ProteinsDrug Evaluation, PreclinicalFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHumansMiceMutationNeoplasm ProteinsNeoplasm TransplantationPapillomaviridaePapillomavirus InfectionsPharmacogeneticsPyrazolesUterine Cervical NeoplasmsConceptsAurora kinase inhibitorsDrug sensitivityWild-type cellsPolo-like kinasesInhibitor-induced apoptosisHigh-throughput drug screensNeck squamous cell carcinomaKinase inhibitorsHPV-negative cell linesSquamous cell carcinomaEffective drug classAurora kinase inhibitionG2-M arrestAurora kinasesHistone deacetylaseAurora inhibitorsCervical cancerTumor sizeCell carcinomaHuman papillomavirusCancer DatabaseDrug classesPharmacogenomic profilingXenograft modelM arrest
2017
Replication Stress Leading to Apoptosis within the S-phase Contributes to Synergism between Vorinostat and AZD1775 in HNSCC Harboring High-Risk TP53 Mutation
Tanaka N, Patel AA, Tang L, Silver NL, Lindemann A, Takahashi H, Jaksik R, Rao X, Kalu NN, Chen TC, Wang J, Frederick MJ, Johnson F, Gleber-Netto FO, Fu S, Kimmel M, Wang J, Hittelman WN, Pickering CR, Myers JN, Osman AA. Replication Stress Leading to Apoptosis within the S-phase Contributes to Synergism between Vorinostat and AZD1775 in HNSCC Harboring High-Risk TP53 Mutation. Clinical Cancer Research 2017, 23: 6541-6554. PMID: 28790110, PMCID: PMC5724758, DOI: 10.1158/1078-0432.ccr-17-0947.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisCarcinoma, Squamous CellCell Cycle ProteinsCell Line, TumorCell ProliferationDNA DamageDNA ReplicationDrug SynergismFemaleHead and Neck NeoplasmsHistone Deacetylase InhibitorsHumansHydroxamic AcidsMiceMutationNuclear ProteinsPhosphorylationProtein-Tyrosine KinasesPyrazolesPyrimidinesPyrimidinonesRisk FactorsS PhaseSquamous Cell Carcinoma of Head and NeckTumor Suppressor Protein p53VorinostatConceptsOrthotopic mouse modelHNSCC cellsOral cancerMouse modelNeck squamous cell carcinomaSquamous cell carcinomaCombination of vorinostatProlongs animal survivalHNSCC cell linesClin Cancer ResClonogenic survival assaysAdvanced HNSCCAdvanced headStandard therapyCell carcinomaCure rateEffective therapyClinical investigationCell cycleP53 mutationsTumor growthVorinostatAnimal survivalAZD1775Cancer ResDistinct 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 gene