2024
Immune infiltration at the primary tumor is associated with clinical outcome of patients with extranodal extension of lymph node metastasis in oral cancer
Michikawa C, Gleber-Netto F, Pickering C, Rao X, Wang J, Sikora A, Myers J, Frederick M. Immune infiltration at the primary tumor is associated with clinical outcome of patients with extranodal extension of lymph node metastasis in oral cancer. Oral Oncology 2024, 153: 106729. PMID: 38663156, DOI: 10.1016/j.oraloncology.2024.106729.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedCarcinoma, Squamous CellExtranodal ExtensionFemaleHumansLymphatic MetastasisMaleMiddle AgedMouth NeoplasmsPrognosisConceptsOral cavity squamous cell carcinomaAssociated with clinical outcomesExtranodal extensionLymph node metastasisImmune infiltrationImmune infiltration statusOverall survivalPrimary tumorNode metastasisOral cancerInfiltration statusClinical outcomes of OSCC patientsExtension of lymph node metastasesAssociated with clinical outcomes of patientsAssociated with OS rateLocally advanced oral cancerClinical outcomes of patientsOutcome of OSCC patientsAssociated with poor overall survivalImmune infiltration of tumorsLow immune infiltrationNode negative tumorsAdvanced oral cancerHuman papillomavirus-negativeInfiltration of tumors
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 ResearchMeSH KeywordsCarcinoma, Squamous CellCell Line, TumorCisplatinHead and Neck NeoplasmsHumansPapillomavirus InfectionsSquamous Cell Carcinoma of Head and NeckTumor Suppressor Protein p53ConceptsHPV-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
Mutant p53 drives an immune cold tumor immune microenvironment in oral squamous cell carcinoma
Shi Y, Xie T, Wang B, Wang R, Cai Y, Yuan B, Gleber-Netto FO, Tian X, Rodriguez-Rosario AE, Osman AA, Wang J, Pickering CR, Ren X, Sikora AG, Myers JN, Rangel R. Mutant p53 drives an immune cold tumor immune microenvironment in oral squamous cell carcinoma. Communications Biology 2022, 5: 757. PMID: 35902768, PMCID: PMC9334280, DOI: 10.1038/s42003-022-03675-4.Peer-Reviewed Original ResearchMeSH KeywordsCarcinoma, Squamous CellGenes, p53Head and Neck NeoplasmsHumansMouth NeoplasmsSquamous Cell Carcinoma of Head and NeckTumor MicroenvironmentTumor Suppressor Protein p53ConceptsOral cavity squamous cell carcinomaTumor immune microenvironmentCold tumor immune microenvironmentSquamous cell carcinomaICI therapyOSCC modelCell carcinomaImmune microenvironmentCold tumorsCell death protein 1 (PD-1) inhibitorsCancer cell-intrinsic mechanismsImmune checkpoint inhibitor therapyOral squamous cell carcinomaCheckpoint inhibitor therapyCombination ICI treatmentEffective immunotherapeutic approachesInterferon genes (STING) agonistImmunosuppressive M2 macrophagesProtein 1 inhibitorTobacco-associated cancersICI responsivenessICI treatmentCell-intrinsic mechanismsImmunotherapeutic approachesInhibitor therapyFusobacterium 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 patientsp16 Represses DNA Damage Repair via a Novel Ubiquitin-Dependent Signaling Cascade
Molkentine DP, Molkentine JM, Bridges KA, Valdecanas DR, Dhawan A, Bahri R, Hefner AJ, Kumar M, Yang L, Abdelhakiem M, Pifer PM, Sandulache V, Sheth A, Beadle BM, Thames HD, Mason KA, Pickering CR, Meyn RE, Skinner HD. p16 Represses DNA Damage Repair via a Novel Ubiquitin-Dependent Signaling Cascade. Cancer Research 2022, 82: 916-928. PMID: 34965932, PMCID: PMC9136619, DOI: 10.1158/0008-5472.can-21-2101.Peer-Reviewed Original ResearchMeSH KeywordsCarcinoma, Squamous CellCarrier ProteinsCyclin-Dependent Kinase Inhibitor p16DNA DamageDNA, ViralHead and Neck NeoplasmsHumansPapillomaviridaePapillomavirus InfectionsSignal TransductionSquamous Cell Carcinoma of Head and NeckTumor Suppressor ProteinsUbiquitinUbiquitin-Protein LigasesUbiquitin-Specific Peptidase 7ConceptsUbiquitin-specific protease 7DNA damage repairDamage repairHPV-positive tumorsTranscription factor Sp1Human papillomavirusFactor Sp1Neck squamous cell carcinoma cellsDNA-damaging therapiesRenders cellsHomologous recombinationSignaling cascadesHPV-negative diseaseSquamous cell carcinoma cellsHPV-negative counterpartsHPV-positive diseaseSquamous cell carcinomaUSP7 inhibitorsDNA damageHPV-negative HNSCCFunctional roleDegradation pathwayHPV positivityPathwayUndiscovered pathwaysGenetic Changes Driving Immunosuppressive Microenvironments in Oral Premalignancy
Rangel R, Pickering CR, Sikora AG, Spiotto MT. Genetic Changes Driving Immunosuppressive Microenvironments in Oral Premalignancy. Frontiers In Immunology 2022, 13: 840923. PMID: 35154165, PMCID: PMC8829003, DOI: 10.3389/fimmu.2022.840923.Peer-Reviewed Original ResearchMeSH KeywordsCarcinoma, Squamous CellHumansMouth NeoplasmsPrecancerous ConditionsTumor MicroenvironmentConceptsOral premalignant lesionsImmunosuppressive microenvironmentProgression of OPLsOral cavity cancerGenomic alterationsImmune microenvironmentOral cancerOSCC progressionInflammatory environmentPremalignant lesionsSpecific genomic changesOral premalignancyTherapeutic approachesNovel biomarkersMalignant transformationMicroenvironmental changesCancerProgressionGenomic changesMicroenvironmentAlterationsGenetic changesPremalignancyTherapyLesions
2019
Genetics and penile cancer: recent developments and implications.
Chahoud J, Pickering CR, Pettaway CA. Genetics and penile cancer: recent developments and implications. Current Opinion In Urology 2019, 29: 364-370. PMID: 31045928, DOI: 10.1097/mou.0000000000000640.Peer-Reviewed Original ResearchConceptsPenile squamous cell carcinomaSquamous cell carcinomaCell carcinomaGene alterationsMultiple squamous cell carcinomasSimilar tumour mutational burdenRecurrent gene alterationsTargetable gene alterationsPD-1 inhibitionOngoing clinical trialsTumor mutational burdenTumor suppressor gene alterationsDifferent organ sitesPenile cancerHuman papillomavirusRare tumorClinical trialsNovel agentsLarge cohortMutational burdenTrial designOrgan sitesPSCC casesPositive expressionRNA signatureIdentification 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 analysisCarcinomaPatientsMarkersPredicting 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 ResearchMeSH KeywordsCarcinoma, Squamous CellHead and Neck NeoplasmsHumansMicroRNAsPapillomavirus InfectionsSquamous Cell Carcinoma of Head and NeckConceptsHigh-risk patient populationNeck squamous cell carcinomaFive-miRNA signatureSquamous cell carcinomaNovel miRNA signatureCell carcinomaClinical variablesHuman papillomavirusInferior outcomesPatient populationNeck cancerTreatment strategiesPredicting OutcomeMiRNA signatureNegative headOutcomesPatientsCarcinomaPapillomavirusCancerHead
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 arrestHigh-Risk TP53 Mutations Are Associated with Extranodal Extension in Oral Cavity Squamous Cell Carcinoma
Sandulache VC, Michikawa C, Kataria P, Gleber-Netto FO, Bell D, Trivedi S, Rao X, Wang J, Zhao M, Jasser S, Myers JN, Pickering CR. High-Risk TP53 Mutations Are Associated with Extranodal Extension in Oral Cavity Squamous Cell Carcinoma. Clinical Cancer Research 2018, 24: 1727-1733. PMID: 29330202, PMCID: PMC5884733, DOI: 10.1158/1078-0432.ccr-17-0721.Peer-Reviewed Original ResearchConceptsOral cavity squamous cell carcinomaExtranodal extensionPrimary tumorDisease-free survivalPoor prognostic factorProspective clinical trialsSquamous cell carcinomaAggressive biological phenotypeClin Cancer ResHigh-risk mutationsPersonalized treatment decisionsWild-type TP53ENE statusOSCC dataPN0 tumorsCancer Genome AtlasLymph nodesPrognostic factorsClinical outcomesInstitutional cohortCell carcinomaClinical trialsPoor survivalTreatment decisionsTreatment selectionGenomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas
Campbell JD, Yau C, Bowlby R, Liu Y, Brennan K, Fan H, Taylor AM, Wang C, Walter V, Akbani R, Byers LA, Creighton CJ, Coarfa C, Shih J, Cherniack AD, Gevaert O, Prunello M, Shen H, Anur P, Chen J, Cheng H, Hayes DN, Bullman S, Pedamallu CS, Ojesina AI, Sadeghi S, Mungall KL, Robertson AG, Benz C, Schultz A, Kanchi RS, Gay CM, Hegde A, Diao L, Wang J, Ma W, Sumazin P, Chiu HS, Chen TW, Gunaratne P, Donehower L, Rader JS, Zuna R, Al-Ahmadie H, Lazar AJ, Flores ER, Tsai KY, Zhou JH, Rustgi AK, Drill E, Shen R, Wong CK, Network T, Caesar-Johnson S, Demchok J, Felau I, Kasapi M, Ferguson M, Hutter C, Sofia H, Tarnuzzer R, Wang Z, Yang L, Zenklusen J, Zhang J, Chudamani S, Liu J, Lolla L, Naresh R, Pihl T, Sun Q, Wan Y, Wu Y, Cho J, DeFreitas T, Frazer S, Gehlenborg N, Getz G, Heiman D, Kim J, Lawrence M, Lin P, Meier S, Noble M, Saksena G, Voet D, Zhang H, Bernard B, Chambwe N, Dhankani V, Knijnenburg T, Kramer R, Leinonen K, Liu Y, Miller M, Reynolds S, Shmulevich I, Thorsson V, Zhang W, Akbani R, Broom B, Hegde A, Ju Z, Kanchi R, Korkut A, Li J, Liang H, Ling S, Liu W, Lu Y, Mills G, Ng K, Rao A, Ryan M, Wang J, Weinstein J, Zhang J, Abeshouse A, Armenia J, Chakravarty D, Chatila W, de Bruijn I, Gao J, Gross B, Heins Z, Kundra R, La K, Ladanyi M, Luna A, Nissan M, Ochoa A, Phillips S, Reznik E, Sanchez-Vega F, Sander C, Schultz N, Sheridan R, Sumer S, Sun Y, Taylor B, Wang J, Zhang H, Anur P, Peto M, Spellman P, Benz C, Stuart J, Wong C, Yau C, Hayes D, Parker J, Wilkerson M, Ally A, Balasundaram M, Bowlby R, Brooks D, Carlsen R, Chuah E, Dhalla N, Holt R, Jones S, Kasaian K, Lee D, Ma Y, Marra M, Mayo M, Moore R, Mungall A, Mungall K, Robertson A, Sadeghi S, Schein J, Sipahimalani P, Tam A, Thiessen N, Tse K, Wong T, Berger A, Beroukhim R, Cherniack A, Cibulskis C, Gabriel S, Gao G, Ha G, Meyerson M, Schumacher S, Shih J, Kucherlapati M, Kucherlapati R, Baylin S, Cope L, Danilova L, Bootwalla M, Lai P, Maglinte D, Van Den Berg D, Weisenberger D, Auman J, Balu S, Bodenheimer T, Fan C, Hoadley K, Hoyle A, Jefferys S, Jones C, Meng S, Mieczkowski P, Mose L, Perou A, Perou C, Roach J, Shi Y, Simons J, Skelly T, Soloway M, Tan D, Veluvolu U, Fan H, Hinoue T, Laird P, Shen H, Zhou W, Bellair M, Chang K, Covington K, Creighton C, Dinh H, Doddapaneni H, Donehower L, Drummond J, Gibbs R, Glenn R, Hale W, Han Y, Hu J, Korchina V, Lee S, Lewis L, Li W, Liu X, Morgan M, Morton D, Muzny D, Santibanez J, Sheth M, Shinbrot E, Wang L, Wang M, Wheeler D, Xi L, Zhao F, Hess J, Appelbaum E, Bailey M, Cordes M, Ding L, Fronick C, Fulton L, Fulton R, Kandoth C, Mardis E, McLellan M, Miller C, Schmidt H, Wilson R, Crain D, Curley E, Gardner J, Lau K, Mallery D, Morris S, Paulauskis J, Penny R, Shelton C, Shelton T, Sherman M, Thompson E, Yena P, Bowen J, Gastier-Foster J, Gerken M, Leraas K, Lichtenberg T, Ramirez N, Wise L, Zmuda E, Corcoran N, Costello T, Hovens C, Carvalho A, de Carvalho A, Fregnani J, Longatto-Filho A, Reis R, Scapulatempo-Neto C, Silveira H, Vidal D, Burnette A, Eschbacher J, Hermes B, Noss A, Singh R, Anderson M, Castro P, Ittmann M, Huntsman D, Kohl B, Le X, Thorp R, Andry C, Duffy E, Lyadov V, Paklina O, Setdikova G, Shabunin A, Tavobilov M, McPherson C, Warnick R, Berkowitz R, Cramer D, Feltmate C, Horowitz N, Kibel A, Muto M, Raut C, Malykh A, Barnholtz-Sloan J, Barrett W, Devine K, Fulop J, Ostrom Q, Shimmel K, Wolinsky Y, Sloan A, De Rose A, Giuliante F, Goodman M, Karlan B, Hagedorn C, Eckman J, Harr J, Myers J, Tucker K, Zach L, Deyarmin B, Hu H, Kvecher L, Larson C, Mural R, Somiari S, Vicha A, Zelinka T, Bennett J, Iacocca M, Rabeno B, Swanson P, Latour M, Lacombe L, Têtu B, Bergeron A, McGraw M, Staugaitis S, Chabot J, Hibshoosh H, Sepulveda A, Su T, Wang T, Potapova O, Voronina O, Desjardins L, Mariani O, Roman-Roman S, Sastre X, Stern M, Cheng F, Signoretti S, Berchuck A, Bigner D, Lipp E, Marks J, McCall S, McLendon R, Secord A, Sharp A, Behera M, Brat D, Chen A, Delman K, Force S, Khuri F, Magliocca K, Maithel S, Olson J, Owonikoko T, Pickens A, Ramalingam S, Shin D, Sica G, Van Meir E, Zhang H, Eijckenboom W, Gillis A, Korpershoek E, Looijenga L, Oosterhuis W, Stoop H, van Kessel K, Zwarthoff E, Calatozzolo C, Cuppini L, Cuzzubbo S, DiMeco F, Finocchiaro G, Mattei L, Perin A, Pollo B, Chen C, Houck J, Lohavanichbutr P, Hartmann A, Stoehr C, Stoehr R, Taubert H, Wach S, Wullich B, Kycler W, Murawa D, Wiznerowicz M, Chung K, Edenfield W, Martin J, Baudin E, Bubley G, Bueno R, De Rienzo A, Richards W, Kalkanis S, Mikkelsen T, Noushmehr H, Scarpace L, Girard N, Aymerich M, Campo E, Giné E, Guillermo A, Van Bang N, Hanh P, Phu B, Tang Y, Colman H, Evason K, Dottino P, Martignetti J, Gabra H, Juhl H, Akeredolu T, Stepa S, Hoon D, Ahn K, Kang K, Beuschlein F, Breggia A, Birrer M, Bell D, Borad M, Bryce A, Castle E, Chandan V, Cheville J, Copland J, Farnell M, Flotte T, Giama N, Ho T, Kendrick M, Kocher J, Kopp K, Moser C, Nagorney D, O’Brien D, O’Neill B, Patel T, Petersen G, Que F, Rivera 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S, Schadendorf D, Couce M, Graefen M, Huland H, Sauter G, Schlomm T, Simon R, Tennstedt P, Olabode O, Nelson M, Bathe O, Carroll P, Chan J, Disaia P, Glenn P, Kelley R, Landen C, Phillips J, Prados M, Simko J, Smith-McCune K, VandenBerg S, Roggin K, Fehrenbach A, Kendler A, Sifri S, Steele R, Jimeno A, Carey F, Forgie I, Mannelli M, Carney M, Hernandez B, Campos B, Herold-Mende C, Jungk C, Unterberg A, von Deimling A, Bossler A, Galbraith J, Jacobus L, Knudson M, Knutson T, Ma D, Milhem M, Sigmund R, Godwin A, Madan R, Rosenthal H, Adebamowo C, Adebamowo S, Boussioutas A, Beer D, Giordano T, Mes-Masson A, Saad F, Bocklage T, Landrum L, Mannel R, Moore K, Moxley K, Postier R, Walker J, Zuna R, Feldman M, Valdivieso F, Dhir R, Luketich J, Pinero E, Quintero-Aguilo M, Carlotti C, Dos Santos J, Kemp R, Sankarankuty A, Tirapelli D, Catto J, Agnew K, Swisher E, Creaney J, Robinson B, Shelley C, Godwin E, Kendall S, Shipman C, Bradford C, Carey T, Haddad A, Moyer J, Peterson L, Prince M, Rozek L, Wolf G, Bowman R, Fong K, Yang I, Korst R, Rathmell W, Fantacone-Campbell J, Hooke J, Kovatich A, Shriver C, DiPersio J, Drake B, Govindan R, Heath S, Ley T, Van Tine B, Westervelt P, Rubin M, Lee J, Aredes N, Mariamidze A, Stuart J, Laird P, Hoadley K, Weinstein J, Peto M, Pickering C, Chen Z, Van Waes C. Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas. Cell Reports 2018, 23: 194-212.e6. PMID: 29617660, PMCID: PMC6002769, DOI: 10.1016/j.celrep.2018.03.063.Peer-Reviewed Original ResearchConceptsChromosomal copy number alterationsSquamous cell carcinomaRAS-MAPK pathwayChromatin modifiersGenomic integrityCopy number alterationsAlternative promotersHuman papillomavirusDNA mutationsPathway networkAberrant methylationCell stemnessHarbor mutationsOxidative damageAtlas studyMesenchymal differentiationCell signatureMutationsMolecular featuresImmune checkpointsImmune therapySquamous carcinomaCell carcinomaImmunoregulatory moleculesTherapeutic approachesCDKN2A/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
Comprehensive Genomic Profiling of Metastatic Squamous Cell Carcinoma of the Anal Canal
Morris V, Rao X, Pickering C, Foo WC, Rashid A, Eterovic K, Kim T, Chen K, Wang J, Shaw K, Eng C. Comprehensive Genomic Profiling of Metastatic Squamous Cell Carcinoma of the Anal Canal. Molecular Cancer Research 2017, 15: 1542-1550. PMID: 28784613, PMCID: PMC5991496, DOI: 10.1158/1541-7786.mcr-17-0060.Peer-Reviewed Original ResearchMeSH KeywordsAgedAged, 80 and overAnimalsAnus NeoplasmsCarcinoma, Squamous CellClass I Phosphatidylinositol 3-KinasesDNA-Binding ProteinsExome SequencingFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHumansMiceMiddle AgedMutationNeoplasm MetastasisNeoplasm ProteinsNeoplasm TransplantationPapillomavirus InfectionsPatient-Specific ModelingTumor Suppressor Protein p53ConceptsMetastatic SCCAHuman papillomavirusMutation burdenPatient-derived xenograft modelsAvailable frozen tissueDistinct tumor subpopulationsAnti-EGFR treatmentTumor mutation burdenRare gastrointestinal malignancySquamous cell carcinomaNovel therapeutic approachesComprehensive molecular profilingLow mutation burdenComprehensive genomic characterizationMajority of casesWhole-exome sequencingGene mutation frequencyGastrointestinal malignanciesAdditional patientsAnal canalAnnual incidenceValidation cohortCell carcinomaStandard treatmentPrior infectionReplication 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 geneAPOBEC3A 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-kinasePrevalence of promoter mutations in the TERT gene in oral cavity squamous cell carcinoma
Chang K, Wang C, Pickering CR, Huang Y, Tsai C, Tsang N, Kao H, Cheng M, Myers JN. Prevalence of promoter mutations in the TERT gene in oral cavity squamous cell carcinoma. Head & Neck 2017, 39: 1131-1137. PMID: 28230921, DOI: 10.1002/hed.24728.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overCarcinoma, Squamous CellCohort StudiesDisease ProgressionDisease-Free SurvivalFemaleGene Expression Regulation, NeoplasticHumansKaplan-Meier EstimateMaleMiddle AgedMouth NeoplasmsMutationPrevalencePromoter Regions, GeneticReal-Time Polymerase Chain ReactionRetrospective StudiesRisk AssessmentStatistics, NonparametricSurvival AnalysisTaiwanTelomeraseConceptsOral cavity squamous cell carcinomaSquamous cell carcinomaTERT promoter mutationsAdjacent normal tissuesPromoter mutationsSomatic TERT promoter mutationsNormal tissuesC228T mutationTelomerase reverse transcriptase (TERT) promoterT mutationSCC tumor tissuesHuman telomerase reverse transcriptase (hTERT) promoterC250T mutationsReverse transcriptase promoterCell carcinomaSCC tumorsC228TTumor tissueTERT activityBetel nutTERT promoterTissuePresent studyMutationsSanger methodMutations 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