2022
p16 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
2020
Targeting DNA damage response in head and neck cancers through abrogation of cell cycle checkpoints
Molkentine JM, Molkentine DP, Bridges KA, Xie T, Yang L, Sheth A, Heffernan TP, Clump DA, Faust AZ, Ferris RL, Myers JN, Frederick MJ, Mason KA, Meyn RE, Pickering CR, Skinner HD. Targeting DNA damage response in head and neck cancers through abrogation of cell cycle checkpoints. International Journal Of Radiation Biology 2020, 97: 1121-1128. PMID: 32073931, PMCID: PMC7483862, DOI: 10.1080/09553002.2020.1730014.Peer-Reviewed Original ResearchConceptsHPV statusHPV(-) cellsNeck cancerPARP inhibitionPCR arrayDNA repair genesSignificant radiosensitizationBeneficial treatment optionPARP inhibitor niraparibEffective treatment strategiesHNSCC cell linesNormal tissue toxicityRepair genesShRNA screenRole of p16HPV- tumorsHNSCC xenograftsTreatment optionsTreatment modalitiesTreatment strategiesTherapeutic ratioLimited progressionHPVP16 expressionNiraparib
2017
Replication 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 Res
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
Chk1/2 Inhibition Overcomes the Cisplatin Resistance of Head and Neck Cancer Cells Secondary to the Loss of Functional p53
Gadhikar MA, Sciuto MR, Alves MV, Pickering CR, Osman AA, Neskey DM, Zhao M, Fitzgerald AL, Myers JN, Frederick MJ. Chk1/2 Inhibition Overcomes the Cisplatin Resistance of Head and Neck Cancer Cells Secondary to the Loss of Functional p53. Molecular Cancer Therapeutics 2013, 12: 1860-1873. PMID: 23839309, PMCID: PMC3955083, DOI: 10.1158/1535-7163.mct-13-0157.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Squamous CellCell Line, TumorCellular SenescenceCheckpoint Kinase 1Checkpoint Kinase 2CisplatinDNA DamageDrug Resistance, NeoplasmHead and Neck NeoplasmsHumansMitosisMolecular Targeted TherapyMutationProtein Kinase InhibitorsProtein KinasesSignal TransductionThiophenesTumor Suppressor Protein p53UreaConceptsHNSCC cellsCisplatin resistanceAdvanced stage squamous cell carcinomaStage squamous cell carcinomaSquamous cell carcinomaTreatment of HNSCCP53 mutant tumorsLoss of TP53Neck cancer cellsWild-type TP53Multimodality therapyStandard therapyTreatment failureCell carcinomaPreclinical dataHNSCC tumorsTherapeutic advantageTP53 mutationsP53 mutationsTargeted inhibitionPersonalized approachHNSCCP53-deficient cellsKinase inhibitorsSynthetic lethal manner
2010
DNA Damage Drives an Activin A–Dependent Induction of Cyclooxygenase-2 in Premalignant Cells and Lesions
Fordyce C, Fessenden T, Pickering C, Jung J, Singla V, Berman H, Tlsty T. DNA Damage Drives an Activin A–Dependent Induction of Cyclooxygenase-2 in Premalignant Cells and Lesions. Cancer Prevention Research 2010, 3: 190-201. PMID: 20028875, PMCID: PMC2954106, DOI: 10.1158/1940-6207.capr-09-0229.Peer-Reviewed Original ResearchMeSH KeywordsActivinsAtaxia Telangiectasia Mutated ProteinsBlotting, WesternBreast NeoplasmsCarcinoma in SituCarcinoma, Ductal, BreastCell Cycle ProteinsCyclin-Dependent Kinase Inhibitor p16Cyclooxygenase 2DNA DamageDNA-Binding ProteinsEnzyme-Linked Immunosorbent AssayFemaleGene ExpressionGene Expression ProfilingHumansImmunohistochemistryNeoplasm ProteinsOligonucleotide Array Sequence AnalysisPrecancerous ConditionsProtein Serine-Threonine KinasesRetinoblastoma ProteinReverse Transcriptase Polymerase Chain ReactionSignal TransductionTelomereTelomeric Repeat Binding Protein 2Tumor Suppressor Protein p53Tumor Suppressor ProteinsConceptsCOX-2 expressionCyclooxygenase-2Activin AEpithelial cellsHigh COX-2 expressionPoor clinical outcomeCOX-2 inhibitionCOX-2 inhibitorsTumor-promoting phenotypeSynthesis of prostaglandinsDNA damageDependent inductionVariant human mammary epithelial cellsBreast epithelial cellsHuman mammary epithelial cellsGastrointestinal complicationsSystemic complicationsClinical outcomesDuctal carcinomaCell cycle arrestSitu lesionsChemopreventative agentMammary epithelial cellsCancer metastasisPremalignant cells