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 AssaysWhole-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
Functionally impactful TP53 mutations are associated with increased risk of extranodal extension in clinically advanced oral squamous cell carcinoma
Gleber‐Netto F, Neskey D, de Mattos Costa A, Kataria P, Rao X, Wang J, Kowalski LP, Pickering CR, Dias‐Neto E, Myers JN. Functionally impactful TP53 mutations are associated with increased risk of extranodal extension in clinically advanced oral squamous cell carcinoma. Cancer 2020, 126: 4498-4510. PMID: 32797678, DOI: 10.1002/cncr.33101.Peer-Reviewed Original ResearchConceptsAdvanced oral squamous cell carcinomaOral squamous cell carcinomaExtranodal extensionSquamous cell carcinomaTP53 mutationsAncillary biomarkersCell carcinomaCancer Genome Atlas (TCGA) cohortPostoperative adjuvant therapyTP53 mutation statusWild-type TP53Adjuvant therapyCancer Genome AtlasCommon genetic eventClinicopathologic characteristicsClinical outcomesP53 protein functionPatient managementTreatment decisionsClinical challengeTherapeutic approachesPatientsMutation statusHeterogeneous groupIncreased chance
2019
Identification of novel diagnostic markers for sinonasal undifferentiated carcinoma
Takahashi Y, Gleber‐Netto F, Bell D, Roberts D, Xie T, Abdelmeguid AS, Pickering C, Myers JN, Hanna EY. Identification of novel diagnostic markers for sinonasal undifferentiated carcinoma. Head & Neck 2019, 41: 2688-2695. PMID: 30932264, DOI: 10.1002/hed.25748.Peer-Reviewed Original ResearchConceptsSinonasal squamous cell carcinomaSinonasal undifferentiated carcinomaUndifferentiated carcinomaDiagnostic markerNew diagnostic molecular markersSquamous cell carcinomaDistinct pathologic entityPotential therapeutic targetNovel diagnostic markerNew diagnostic markersSNSCC patientsNeuroendocrine featuresCell carcinomaHistopathologic markersSquamous lineagePathologic entityUndifferentiated tumorsAggressive cancerTumor specimensTherapeutic targetOncology panelUnsupervised cluster analysisCarcinomaPatientsMarkers
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
APOBEC3A is an oral cancer prognostic biomarker in Taiwanese carriers of an APOBEC deletion polymorphism
Chen TW, Lee CC, Liu H, Wu CS, Pickering CR, Huang PJ, Wang J, Chang IY, Yeh YM, Chen CD, Li HP, Luo JD, Tan BC, Chan TEH, Hsueh C, Chu LJ, Chen YT, Zhang B, Yang CY, Wu CC, Hsu CW, See LC, Tang P, Yu JS, Liao WC, Chiang WF, Rodriguez H, Myers JN, Chang KP, Chang YS. APOBEC3A is an oral cancer prognostic biomarker in Taiwanese carriers of an APOBEC deletion polymorphism. Nature Communications 2017, 8: 465. PMID: 28878238, PMCID: PMC5587710, DOI: 10.1038/s41467-017-00493-9.Peer-Reviewed Original ResearchConceptsOral squamous cell carcinomaSquamous cell carcinomaCell carcinomaTaiwanese oral squamous cell carcinomasClinical prognostic relevanceBetter overall survivalCancer prognostic biomarkersExpression of APOBEC3AOverall survivalPrognostic relevanceTaiwanese patientsPrognostic biomarkerSecond cohortGermline polymorphismsCancer typesProminent cancerMutational profileDeletion polymorphismPatientsCarcinomaMutation signaturesExpressionPolymorphismCohortTumorsIntegrative 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-kinase
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 overexpression
2013
High intratumor genetic heterogeneity is related to worse outcome in patients with head and neck squamous cell carcinoma
Mroz EA, Tward AD, Pickering CR, Myers JN, Ferris RL, Rocco JW. High intratumor genetic heterogeneity is related to worse outcome in patients with head and neck squamous cell carcinoma. Cancer 2013, 119: 3034-3042. PMID: 23696076, PMCID: PMC3735618, DOI: 10.1002/cncr.28150.Peer-Reviewed Original ResearchConceptsMutant-allele tumor heterogeneityNeck squamous cell carcinomaSquamous cell carcinomaHigher mutant allele tumor heterogeneityClinical outcomesCell carcinomaWorse outcomesHigh-risk patientsWorse clinical outcomesOverall survival dataShorter overall survivalAdverse treatment outcomesTumor protein p53 (TP53) mutationsHigh genetic heterogeneityGenetic heterogeneityOverall survivalPrognostic valueAdverse outcomesHuman papillomavirusPatient cohortTreatment outcomesIndividual patientsHigh riskPatientsAdvanced stage
2011
Phosphoproteomic Analysis of Signaling Pathways in Head and Neck Squamous Cell Carcinoma Patient Samples
Frederick MJ, VanMeter AJ, Gadhikar MA, Henderson YC, Yao H, Pickering CC, Williams MD, El-Naggar AK, Sandulache V, Tarco E, Myers JN, Clayman GL, Liotta LA, Petricoin EF, Calvert VS, Fodale V, Wang J, Weber RS. Phosphoproteomic Analysis of Signaling Pathways in Head and Neck Squamous Cell Carcinoma Patient Samples. American Journal Of Pathology 2011, 178: 548-571. PMID: 21281788, PMCID: PMC3070553, DOI: 10.1016/j.ajpath.2010.10.044.Peer-Reviewed Original ResearchMeSH KeywordsBiomarkers, TumorBlotting, WesternCarcinoma, Squamous CellCell Line, TumorCluster AnalysisFemaleHead and Neck NeoplasmsHumansImmunohistochemistryMaleMucous MembraneNeoplasm ProteinsPhosphoproteinsPhosphorylationProtein Array AnalysisProtein Kinase CProteomicsReproducibility of ResultsSignal TransductionConceptsReverse-phase protein microarrayNeck squamous cell carcinomaSquamous cell carcinomaEukaryotic translation initiation factor 4ETranslation initiation factor 4ECell carcinomaInitiation factor 4ESmall molecule inhibitorsSerine 345Phosphoproteomic analysisChk-2Protein kinaseSignaling pathwaysElevated analytesPatient-specific differencesLung cancerBiopsy specimensPromising new strategyProtein microarraysTumor typesTheranostic testsEnd pointPatient samplesTumorsPersonalized therapy