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 outcomes
2022
Combined TRIP13 and Aurora Kinase Inhibition Induces Apoptosis in Human Papillomavirus-Driven Cancers.
Ghosh S, Mazumdar T, Xu W, Powell RT, Stephan C, Shen L, Shah PA, Pickering CR, Myers JN, Wang J, Frederick MJ, Johnson FM. Combined TRIP13 and Aurora Kinase Inhibition Induces Apoptosis in Human Papillomavirus-Driven Cancers. Clinical Cancer Research 2022, 28: 4479-4493. PMID: 35972731, PMCID: PMC9588713, DOI: 10.1158/1078-0432.ccr-22-1627.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphatasesAlphapapillomavirusApoptosisATPases Associated with Diverse Cellular ActivitiesAurora KinasesCell Cycle ProteinsFemaleHumansOncogene Proteins, ViralPapillomaviridaePapillomavirus E7 ProteinsPapillomavirus InfectionsRetinoblastoma ProteinUterine Cervical NeoplasmsConceptsHPV-positive cancer cellsInhibition-induced apoptosisAurora kinase inhibitorsAurora kinase inhibitionCancer cellsKinase inhibitionAbsence of RbViral oncoprotein E7Kinase inhibitorsMitotic exitAAA-ATPaseProtein degradationRb functionMechanisms of sensitivityPathway componentsTRIP13MAD2L1Extensive apoptosisCancer cell linesSquamous cancer cell linesApoptosisCell linesRetinoblastoma expressionBUB1BProtein expression correlatesHigh 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 activityBasalMesenchymalFusobacterium is enriched in oral cancer and promotes induction of programmed death-ligand 1 (PD-L1)
Michikawa C, Gopalakrishnan V, Harrandah AM, Karpinets TV, Garg RR, Chu RA, Park YP, Chukkapallia SS, Yadlapalli N, Erikson-Carter KC, Gleber-Netto FO, Sayour E, Progulske-Fox A, Chan , Wu X, Zhang J, Jobin C, Wargo JA, Pickering CR, Myers JN, Silver N. Fusobacterium is enriched in oral cancer and promotes induction of programmed death-ligand 1 (PD-L1). Neoplasia 2022, 31: 100813. PMID: 35834946, PMCID: PMC9287628, DOI: 10.1016/j.neo.2022.100813.Peer-Reviewed Original ResearchConceptsPD-L1 expressionAdjacent normal tissuesWhole-exome sequencingNormal tissuesNeck cancerOral tongue squamous cell carcinoma patientsTongue squamous cell carcinoma patientsSquamous cell carcinoma patientsTumor samplesPD-L1 mRNA expressionPD-L1 protein expressionOral tongue SCCCell carcinoma patientsOral tongue cancerImmune cell infiltrationPD-L1 mRNATumor immune microenvironmentNeck SCC cell linesNeck cancer cell linesSCC cell linesDevelopment of headCell linesCancer cell linesTongue SCCCarcinoma patients
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-Phe
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 model
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 approach
2018
CDKN2A/p16 deletion in head and neck cancer cells is associated with Cdk2 activation, replication stress, and vulnerability to Chk1 inhibition
Gadhikar MA, Zhang J, Shen L, Rao X, Wang J, Zhao M, Kalu NN, Johnson FM, Byers LA, Heymach J, Hittelman WN, Udayakumar D, Pandita RK, Pandita TK, Pickering CR, Redwood AB, Piwnica-Worms H, Schlacher K, Frederick MJ, Myers JN. CDKN2A/p16 deletion in head and neck cancer cells is associated with Cdk2 activation, replication stress, and vulnerability to Chk1 inhibition. Cancer Research 2018, 78: canres.2802.2017. PMID: 29229598, PMCID: PMC5811346, DOI: 10.1158/0008-5472.can-17-2802.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic AgentsApoptosisBiomarkers, TumorCarcinoma, Squamous CellCell ProliferationCheckpoint Kinase 1Cyclin-Dependent Kinase 2Cyclin-Dependent Kinase Inhibitor p16Cyclin-Dependent Kinase Inhibitor p18DNA ReplicationEnzyme ActivationEnzyme InhibitorsHead and Neck NeoplasmsHumansS PhaseSequence DeletionTumor Cells, CulturedConceptsBiomarker-driven strategiesHNSCC patientsS-phase arrestEarly S-phase arrestCDKN2A/Neck squamous cell carcinoma cell linesSquamous cell carcinoma cell linesSingle-agent activityCell carcinoma cell linesCell linesHypersensitive cellsCarcinoma cell linesCdk2 activationHNSCC cellsDrug dosesCertain tumorsCancer ResCopy number lossCausative factorsHypersensitivityCHK inhibitorsPanel medianMonotherapyDrug ICReplication stress
2017
Genomic characterization of human papillomavirus-positive and -negative human squamous cell cancer cell lines
Kalu NN, Mazumdar T, Peng S, Shen L, Sambandam V, Rao X, Xi Y, Li L, Qi Y, Gleber-Netto FO, Patel A, Wang J, Frederick MJ, Myers JN, Pickering CR, Johnson FM. Genomic characterization of human papillomavirus-positive and -negative human squamous cell cancer cell lines. Oncotarget 2017, 5: 86369-86383. PMID: 29156801, PMCID: PMC5689691, DOI: 10.18632/oncotarget.21174.Peer-Reviewed Original ResearchIntegrative Analysis Identifies a Novel AXL–PI3 Kinase–PD-L1 Signaling Axis Associated with Radiation Resistance in Head and Neck Cancer
Skinner HD, Giri U, Yang LP, Kumar M, Liu Y, Story MD, Pickering CR, Byers LA, Williams MD, Wang J, Shen L, Yoo SY, Fan YH, Molkentine DP, Beadle BM, Meyn RE, Myers JN, Heymach JV. Integrative Analysis Identifies a Novel AXL–PI3 Kinase–PD-L1 Signaling Axis Associated with Radiation Resistance in Head and Neck Cancer. Clinical Cancer Research 2017, 23: 2713-2722. PMID: 28476872, PMCID: PMC5457365, DOI: 10.1158/1078-0432.ccr-16-2586.Peer-Reviewed Original ResearchMeSH KeywordsAgedAxl Receptor Tyrosine KinaseB7-H1 AntigenBiomarkers, TumorCarcinoma, Squamous CellCell Line, TumorFemaleGene Expression Regulation, NeoplasticHead and Neck NeoplasmsHumansLymphocytes, Tumor-InfiltratingMaleMiddle AgedPapillomaviridaePhosphatidylinositol 3-KinasesProteomicsProto-Oncogene ProteinsRadiation ToleranceReceptor Protein-Tyrosine KinasesRNA, MessengerSignal TransductionConceptsPD-L1HPV-negative HNSCC tumorsNeck squamous cell carcinomaCell linesHPV-negative HNSCC cell linesLocal failureLocal treatment failurePD-L1 axisPD-L1 expressionTumor-infiltrating lymphocytesSquamous cell carcinomaHuman papilloma virusLow expression groupActivation of AxlHNSCC cell linesClin Cancer ResNegative cell linesTreatment failureCell carcinomaPapilloma virusHNSCC tumorsExpression groupMultivariate analysisMRNA expression analysisPI3-kinaseMutations of the LIM protein AJUBA mediate sensitivity of head and neck squamous cell carcinoma to treatment with cell-cycle inhibitors
Zhang M, Singh R, Peng S, Mazumdar T, Sambandam V, Shen L, Tong P, Li L, Kalu NN, Pickering CR, Frederick M, Myers JN, Wang J, Johnson FM. Mutations of the LIM protein AJUBA mediate sensitivity of head and neck squamous cell carcinoma to treatment with cell-cycle inhibitors. Cancer Letters 2017, 392: 71-82. PMID: 28126323, PMCID: PMC5404895, DOI: 10.1016/j.canlet.2017.01.024.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsApoptosisCarcinoma, Squamous CellCell Cycle ProteinsCell Line, TumorCell ProliferationCheckpoint Kinase 1Checkpoint Kinase 2Dose-Response Relationship, DrugG2 Phase Cell Cycle CheckpointsGenotypeHead and Neck NeoplasmsHumansLIM Domain ProteinsMice, NudeMolecular Targeted TherapyMutationNuclear ProteinsPhenotypeProtein Kinase InhibitorsProtein Serine-Threonine KinasesProtein-Tyrosine KinasesProto-Oncogene ProteinsPteridinesPyrazolesPyrimidinesPyrimidinonesRas ProteinsRNA InterferenceSignal TransductionSmad4 ProteinSquamous Cell Carcinoma of Head and NeckThiophenesTime FactorsTransfectionTumor BurdenUreaXenograft Model Antitumor AssaysConceptsPolo-like kinase 1Cell linesLIM protein AjubaHNSCC cell linesInhibitor-induced apoptosisProtein expressionCell cycle inhibitorsCell cycle arrestKnockdown of PLK1Neck squamous cell carcinomaAjubaExogenous expressionNeck squamous cell carcinoma (HNSCC) tumorsSquamous cell carcinoma tumorsKinase 1HNSCC mouse modelSquamous cell carcinomaSubstrate inhibitionHigher drug dosesPotential candidate biomarkersGenomic alterationsMitotic inhibitorsPLK1 inhibitionSensitive cell linesMutations
2016
Proteomic Profiling Identifies PTK2/FAK as a Driver of Radioresistance in HPV-negative Head and Neck Cancer
Skinner HD, Giri U, Yang L, Woo SH, Story MD, Pickering CR, Byers LA, Williams MD, El-Naggar A, Wang J, Diao L, Shen L, Fan YH, Molkentine DP, Beadle BM, Meyn RE, Myers JN, Heymach JV. Proteomic Profiling Identifies PTK2/FAK as a Driver of Radioresistance in HPV-negative Head and Neck Cancer. Clinical Cancer Research 2016, 22: 4643-4650. PMID: 27036135, PMCID: PMC5061056, DOI: 10.1158/1078-0432.ccr-15-2785.Peer-Reviewed Original ResearchConceptsHPV-negative HNSCC cell linesHPV-negative HNSCCHNSCC cell linesTargetable biomarkersHuman papillomavirusIndependent cohortCandidate biomarkersPoor disease-free survivalNeck squamous cell carcinomaBiomarker of radioresistanceDisease-free survivalSquamous cell carcinomaDisease-related mortalityMerit further evaluationCell linesFAK inhibitionG2-M arrestFocal adhesion kinaseAdvanced HNSCCWorse DFSCancer Genome AtlasCell carcinomaPharmacologic blockadeCancer subgroupsFAK overexpressionHuman epidermal growth factor receptor 2/neu as a novel therapeutic target in sinonasal undifferentiated carcinoma
Takahashi Y, Lee J, Pickering C, Bell D, Jiffar TW, Myers JN, Hanna EY, Kupferman ME. Human epidermal growth factor receptor 2/neu as a novel therapeutic target in sinonasal undifferentiated carcinoma. Head & Neck 2016, 38: e1926-e1934. PMID: 26752332, PMCID: PMC6453572, DOI: 10.1002/hed.24350.Peer-Reviewed Original ResearchConceptsHuman epidermal growth factor receptor 2Sinonasal undifferentiated carcinomaEpidermal growth factor receptor 2Growth factor receptor 2Potential therapeutic targetFactor receptor 2Cell linesGrowth inhibitionProtein expression levelsCell growth inhibitionMethylthiazol tetrazoliumMultimodal therapyHER2 inhibitionUndifferentiated carcinomaNovel therapiesAggressive cancerNew therapiesReceptor 2Therapeutic targetFlank modelClonogenic assayWestern blottingWhole-genome single nucleotide polymorphism (SNP) analysisTherapyERBB2 gene
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 speciesOutcomes
2014
HRAS mutations and resistance to the epidermal growth factor receptor tyrosine kinase inhibitor erlotinib in head and neck squamous cell carcinoma cells
Hah JH, Zhao M, Pickering CR, Frederick MJ, Andrews GA, Jasser SA, Fooshee DR, Milas ZL, Galer C, Sano D, William WN, Kim E, Heymach J, Byers LA, Papadimitrakopoulou V, Myers JN. HRAS mutations and resistance to the epidermal growth factor receptor tyrosine kinase inhibitor erlotinib in head and neck squamous cell carcinoma cells. Head & Neck 2014, 36: 1547-1554. PMID: 24123531, PMCID: PMC4010580, DOI: 10.1002/hed.23499.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlotting, WesternCarcinoma, Squamous CellCell Line, TumorCell ProliferationDown-RegulationDrug Resistance, NeoplasmErlotinib HydrochlorideHead and Neck NeoplasmsHumansMiceMolecular Targeted TherapyMutationProtein Kinase InhibitorsProto-Oncogene Proteins p21(ras)QuinazolinesSensitivity and SpecificitySignal TransductionSquamous Cell Carcinoma of Head and NeckTransfectionConceptsShort hairpin RNACell linesHRAS expressionErlotinib sensitivityErlotinib-sensitive cell linesErlotinib-resistant cell linesErlotinib resistanceHRAS mutationsNeck squamous cell carcinoma cellsEpidermal growth factor receptor tyrosine kinase inhibitorsGrowth factor receptor tyrosine kinase inhibitorsEpidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinibNeck squamous cell carcinoma cell linesSquamous cell carcinoma cellsTyrosine kinase inhibitor erlotinibPanel of headReceptor tyrosine kinase inhibitorsHairpin RNAHNSCC cell linesSquamous cell carcinoma cell linesCell carcinoma cell linesCarcinoma cell linesKinase inhibitor erlotinibTyrosine kinase inhibitorsMutations
2011
Assembly and Initial Characterization of a Panel of 85 Genomically Validated Cell Lines from Diverse Head and Neck Tumor Sites
Zhao M, Sano D, Pickering CR, Jasser SA, Henderson YC, Clayman GL, Sturgis EM, Ow TJ, Lotan R, Carey TE, Sacks PG, Grandis JR, Sidransky D, Heldin NE, Myers JN. Assembly and Initial Characterization of a Panel of 85 Genomically Validated Cell Lines from Diverse Head and Neck Tumor Sites. Clinical Cancer Research 2011, 17: 7248-7264. PMID: 21868764, PMCID: PMC3229662, DOI: 10.1158/1078-0432.ccr-11-0690.Peer-Reviewed Original ResearchConceptsNeck cell linesSquamous cell carcinomaCell carcinomaCell linesTumor siteCutaneous squamous cell carcinomaNeck squamous cell carcinomaNeck tumor sitesHuman papillomavirus (HPV) statusPrimary tumor siteHPV-16 DNAOral leukoplakiaNeck cancerThyroid cancerCystic carcinomaMajor headPreclinical studiesNormal epitheliumDiverse headTissue sitesCarcinomaCancer research communityPrimary keratinocytesCancer therapyDisruptive TP53 Mutation Is Associated with Aggressive Disease Characteristics in an Orthotopic Murine Model of Oral Tongue Cancer
Sano D, Xie TX, Ow TJ, Zhao M, Pickering CR, Zhou G, Sandulache VC, Wheeler DA, Gibbs RA, Caulin C, Myers JN. Disruptive TP53 Mutation Is Associated with Aggressive Disease Characteristics in an Orthotopic Murine Model of Oral Tongue Cancer. Clinical Cancer Research 2011, 17: 6658-6670. PMID: 21903770, PMCID: PMC3207013, DOI: 10.1158/1078-0432.ccr-11-0046.Peer-Reviewed Original ResearchConceptsDisruptive TP53 mutationsCervical lymph node metastasisOral tongue cancerLymph node metastasisOrthotopic murine modelHNSCC cell linesTP53 mutationsNode metastasisTongue cancerMurine modelCell linesTumor growthNeck squamous cell carcinoma cell linesSquamous cell carcinoma cell linesAggressive disease characteristicsCell carcinoma cell linesFaster tumor growthPoor patient outcomesP53 protein expressionTP53 mutation statusBehavior of tumorsWild-type TP53Western blot analysisOral tongueShorter survivalIndividualizing antimetabolic treatment strategies for head and neck squamous cell carcinoma based on TP53 mutational status
Sandulache VC, Skinner HD, Ow TJ, Zhang A, Xia X, Luchak JM, Wong L, Pickering CR, Zhou G, Myers JN. Individualizing antimetabolic treatment strategies for head and neck squamous cell carcinoma based on TP53 mutational status. Cancer 2011, 118: 711-721. PMID: 21720999, PMCID: PMC3188683, DOI: 10.1002/cncr.26321.Peer-Reviewed Original ResearchConceptsMitochondrial respirationGlycolytic dependenceHNSCC cellsAltered tumor cell metabolismGlycolytic inhibitionTumor suppressor geneTumor cell metabolismTP53 mutational statusMitochondrial reserveInhibition of respirationMetabolic shiftCell metabolismCellular resistanceSuppressor geneHNSCC cell linesMutational statusGlycolytic fluxCell linesRespirationNeck squamous cell carcinomaMutationsGlycolysisCellsClonogenic assayRadioresistance