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 outcomesHRAS 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 ResearchMeSH KeywordsAgedHead and Neck NeoplasmsHumansMaleMiddle AgedMutationNeoplasm Recurrence, LocalProto-Oncogene Proteins p21(ras)Squamous Cell Carcinoma of Head and NeckConceptsNeck 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 ResearchMeSH KeywordsGenes, p53Head and Neck NeoplasmsHumansMutationPapillomavirus InfectionsSquamous Cell Carcinoma of Head and NeckTumor Suppressor Protein p53ConceptsNeck 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 NetworkMutant 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 ResearchMeSH KeywordsB7-H1 AntigenCarcinoma, Squamous CellFusobacteriumHead and Neck NeoplasmsHumansMouth NeoplasmsRNA, MessengerRNA, Ribosomal, 16SSquamous Cell Carcinoma of Head and NeckTongue NeoplasmsTumor MicroenvironmentConceptsPD-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 pathways
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 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 ResearchMeSH KeywordsAnimalsCell Line, TumorCell ProliferationGene Expression Regulation, NeoplasticHead and Neck NeoplasmsHumansMaleMice, Inbred C57BLMice, NudeReceptors, Opioid, muSquamous Cell Carcinoma of Head and NeckConceptsMu-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 modelThe mutational landscape of early‐ and typical‐onset oral tongue squamous cell carcinoma
Campbell BR, Chen Z, Faden DL, Agrawal N, Li RJ, Hanna GJ, Iyer NG, Boot A, Rozen SG, Vettore AL, Panda B, Krishnan NM, Pickering CR, Myers JN, Guo X, Kuhs K. The mutational landscape of early‐ and typical‐onset oral tongue squamous cell carcinoma. Cancer 2020, 127: 544-553. PMID: 33146897, PMCID: PMC7891879, DOI: 10.1002/cncr.33309.Peer-Reviewed Original ResearchMeSH KeywordsAdultAge of OnsetAgedAged, 80 and overFemaleHumansMaleMiddle AgedMutationOncogenesSmokingSquamous Cell Carcinoma of Head and NeckTobacco UseYoung AdultConceptsOral tongue squamous cell carcinomaTongue squamous cell carcinomaSquamous cell carcinomaTongue cancerYounger patientsCell carcinomaTobacco useDriver genesOral tongue cancerPatient-related factorsCancer driver genesTongue cancer specimensAge of onsetMutational landscapeSomatic mutationsMutation signaturesYounger birth cohortsSomatic mutational burdenOlder patientsCancer Genome AtlasSmoking ratesMutational burdenCancer specimensMulticenter consortiumBirth cohortFunctionally 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 ResearchMeSH KeywordsBiomarkers, TumorFemaleHumansMaleMiddle AgedMouth NeoplasmsMutationNeoplasm InvasivenessNeoplasm StagingPrognosisSquamous Cell Carcinoma of Head and NeckTumor Suppressor Protein p53ConceptsAdvanced 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 chanceIdentifying 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 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 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
Mutation allele frequency threshold does not affect prognostic analysis using next-generation sequencing in oral squamous cell carcinoma
Ma J, Fu Y, Tu YY, Liu Y, Tan YR, Ju WT, Pickering CR, Myers JN, Zhang ZY, Zhong LP. Mutation allele frequency threshold does not affect prognostic analysis using next-generation sequencing in oral squamous cell carcinoma. BMC Cancer 2018, 18: 758. PMID: 30041611, PMCID: PMC6057048, DOI: 10.1186/s12885-018-4481-8.Peer-Reviewed Original ResearchConceptsOral squamous cell carcinomaSquamous cell carcinomaPrognostic analysisOSCC patientsCell carcinomaMethodsForty-six patientsClinical outcome analysisNext-generation sequencingAllele frequency thresholdWild-type genotypeParaffin-embedded tissuesNon-synonymous mutationsAllele frequenciesClinical outcomesOutcome analysisPatientsPanel of cancerType genotypeSignificant differencesCarcinomaFrequency thresholdNotch1CDKN2AMutationsCASP8