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 ResearchConceptsNeck 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 ResearchConceptsOral 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 therapy
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
2011
Disruptive 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 survivalExome Sequencing of Head and Neck Squamous Cell Carcinoma Reveals Inactivating Mutations in NOTCH1
Agrawal N, Frederick MJ, Pickering CR, Bettegowda C, Chang K, Li RJ, Fakhry C, Xie TX, Zhang J, Wang J, Zhang N, El-Naggar AK, Jasser SA, Weinstein JN, Treviño L, Drummond JA, Muzny DM, Wu Y, Wood LD, Hruban RH, Westra WH, Koch WM, Califano JA, Gibbs RA, Sidransky D, Vogelstein B, Velculescu VE, Papadopoulos N, Wheeler DA, Kinzler KW, Myers JN. Exome Sequencing of Head and Neck Squamous Cell Carcinoma Reveals Inactivating Mutations in NOTCH1. Science 2011, 333: 1154-1157. PMID: 21798897, PMCID: PMC3162986, DOI: 10.1126/science.1206923.Peer-Reviewed Original ResearchMeSH KeywordsCarcinomaCarcinoma, Squamous CellCell Cycle ProteinsCodon, NonsenseExonsF-Box ProteinsF-Box-WD Repeat-Containing Protein 7Gene DosageGenes, p53Genes, Tumor SuppressorHead and Neck NeoplasmsHumansINDEL MutationMutationMutation, MissenseNeoplasms, Squamous CellOligonucleotide Array Sequence AnalysisOncogenesPapillomaviridaePapillomavirus InfectionsReceptor, Notch1Sequence Analysis, DNASmokingSquamous Cell Carcinoma of Head and NeckUbiquitin-Protein LigasesConceptsNeck squamous cell carcinomaSquamous cell carcinomaCell carcinomaHuman papillomavirusHPV-positive tumorsWhole-exome sequencingMore mutationsPrimary tumorCommon cancerMultiple tumorsTobacco useTumor typesTumorsTumor suppressor geneExome sequencingGene copy number analysisNotch1Copy number analysisPatientsCarcinomaInactivating mutationCancerSuppressor geneMutationsGenetic originGlucose, not glutamine, is the dominant energy source required for proliferation and survival of head and neck squamous carcinoma cells
Sandulache VC, Ow TJ, Pickering CR, Frederick MJ, Zhou G, Fokt I, Davis‐Malesevich M, Priebe W, Myers JN. Glucose, not glutamine, is the dominant energy source required for proliferation and survival of head and neck squamous carcinoma cells. Cancer 2011, 117: 2926-2938. PMID: 21692052, PMCID: PMC3135768, DOI: 10.1002/cncr.25868.Peer-Reviewed Original ResearchAdenosine TriphosphateCarcinomaCarcinoma, Squamous CellCell CycleCell Line, TumorCell ProliferationChromatography, LiquidDeoxyglucoseDisease ProgressionGenes, p53GlucoseGlutamineHead and Neck NeoplasmsHumansLactic AcidMass SpectrometryMetabolomicsMetforminNeoplasms, Squamous CellSquamous Cell Carcinoma of Head and NeckTreatment OutcomeTumor Suppressor Protein p53
2001
Is p53 Haploinsufficient for Tumor Suppression? Implications for the p53+/- Mouse Model in Carcinogenicity Testing
Venkatachalam S, Tyner S, Pickering C, Boley S, Recio L, French J, Donehower L. Is p53 Haploinsufficient for Tumor Suppression? Implications for the p53+/- Mouse Model in Carcinogenicity Testing. Toxicologic Pathology 2001, 29: 147-154. PMID: 11695551, DOI: 10.1080/019262301753178555.Peer-Reviewed Original ResearchConceptsEnhanced tumor susceptibilityWild-type p53 alleleP53-deficient miceMouse modelP53 alleleP53 dosageTumor susceptibilityTransgenic mouse modelWild-type littermatesDifferent tumor typesP53 tumor suppressor geneTumor suppressionP53 LOHTumor typesTumorsTumor suppressor geneMiceP53 lossHaploinsufficient tumor suppressorCarcinogenicity testingPreliminary dataOncogenic lesionsCancer formationMechanisms of genotoxicityTumor suppressor