2021
Inhibition of histone acetyltransferase function radiosensitizes CREBBP/EP300 mutants via repression of homologous recombination, potentially targeting a gain of function
Kumar M, Molkentine D, Molkentine J, Bridges K, Xie T, Yang L, Hefner A, Gao M, Bahri R, Dhawan A, Frederick MJ, Seth S, Abdelhakiem M, Beadle BM, Johnson F, Wang J, Shen L, Heffernan T, Sheth A, Ferris RL, Myers JN, Pickering CR, Skinner HD. Inhibition of histone acetyltransferase function radiosensitizes CREBBP/EP300 mutants via repression of homologous recombination, potentially targeting a gain of function. Nature Communications 2021, 12: 6340. PMID: 34732714, PMCID: PMC8566594, DOI: 10.1038/s41467-021-26570-8.Peer-Reviewed Original ResearchMeSH KeywordsAcetylationAnimalsApoptosisBiomarkers, TumorBRCA1 ProteinCell Line, TumorCREB-Binding ProteinE1A-Associated p300 ProteinGain of Function MutationHistone AcetyltransferasesHomologous RecombinationHumansMaleMice, NudeMutationNeoplasmsProtein DomainsSquamous Cell Carcinoma of Head and NeckXenograft Model Antitumor AssaysLow 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 formation
2020
Loss of p53 drives neuron reprogramming in head and neck cancer
Amit M, Takahashi H, Dragomir MP, Lindemann A, Gleber-Netto FO, Pickering CR, Anfossi S, Osman AA, Cai Y, Wang R, Knutsen E, Shimizu M, Ivan C, Rao X, Wang J, Silverman DA, Tam S, Zhao M, Caulin C, Zinger A, Tasciotti E, Dougherty PM, El-Naggar A, Calin GA, Myers JN. Loss of p53 drives neuron reprogramming in head and neck cancer. Nature 2020, 578: 449-454. PMID: 32051587, PMCID: PMC9723538, DOI: 10.1038/s41586-020-1996-3.Peer-Reviewed Original ResearchMeSH KeywordsAdrenergic AntagonistsAdrenergic NeuronsAnimalsCell DivisionCell TransdifferentiationCellular ReprogrammingDisease Models, AnimalDisease ProgressionFemaleHumansMaleMiceMice, Inbred BALB CMicroRNAsMouth NeoplasmsNerve FibersNeuritesReceptors, AdrenergicRetrospective StudiesSensory Receptor CellsTumor MicroenvironmentTumor Suppressor Protein p53Xenograft Model Antitumor AssaysConceptsOral cancerNerve fibersAdrenergic nerve fibersPoor clinical outcomeTrigeminal sensory neuronsLoss of TP53Sensory denervationAdrenergic nervesChemical sympathectomyNerve densitySensory nervesClinical outcomesSolid tumor microenvironmentLoss of p53Neck cancerPharmacological blockadeEndogenous neuronsRetrospective analysisMouse modelSensory neuronsAdrenergic phenotypeAdrenergic receptorsTumor growthTumor progressionTumor microenvironment
2017
Mutations 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
Human 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 ResearchMeSH KeywordsAnimalsCarcinomaCell Line, TumorHumansLapatinibMaleMaxillary Sinus NeoplasmsMiceMice, NudePolymorphism, Single NucleotideQuinazolinesReceptor, ErbB-2Xenograft Model Antitumor AssaysConceptsHuman 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
Evolutionary 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
2013
Coordinated Targeting of the EGFR Signaling Axis by MicroRNA-27a*
Wu X, Bhayani MK, Dodge CT, Nicoloso MS, Chen Y, Yan X, Adachi M, Thomas L, Galer CE, Jiffar T, Pickering CR, Kupferman ME, Myers JN, Calin GA, Lai SY. Coordinated Targeting of the EGFR Signaling Axis by MicroRNA-27a*. Oncotarget 2013, 4: 1388-1398. PMID: 23963114, PMCID: PMC3824521, DOI: 10.18632/oncotarget.1239.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBinding SitesCarcinoma, Squamous CellCell Growth ProcessesCell Line, TumorCell SurvivalDown-RegulationErbB ReceptorsHead and Neck NeoplasmsHumansMiceMicroRNAsProto-Oncogene Proteins c-aktRNA, MessengerSignal TransductionSquamous Cell Carcinoma of Head and NeckTOR Serine-Threonine KinasesXenograft Model Antitumor AssaysConceptsEpidermal growth factor receptorDownregulation of EGFRSolid tumorsTumor growthNeck squamous cell carcinomaMurine orthotopic xenograft modelHNSCC cell viabilityOral cavity cancerMultiple HNSCC cell linesSquamous cell carcinomaStar strandNovel therapeutic optionsNovel miRNAsMultiple solid tumorsOrthotopic xenograft modelOverexpression of EGFRCoordinated regulationHNSCC cell linesCoordinated targetingGrowth factor receptorComplex regulationDirect intratumoral injectionPathway componentsInducible expressionSignaling Axis