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 ResearchConceptsHPV-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
2019
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
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
2015
Evolutionary Action Score of TP53 Coding Variants Is Predictive of Platinum Response in Head and Neck Cancer Patients
Osman AA, Neskey DM, Katsonis P, Patel AA, Ward AM, Hsu TK, Hicks SC, McDonald TO, Ow TJ, Alves MO, Pickering CR, Skinner HD, Zhao M, Sturgis EM, Kies MS, El-Naggar A, Perrone F, Licitra L, Bossi P, Kimmel M, Frederick MJ, Lichtarge O, Myers JN. Evolutionary Action Score of TP53 Coding Variants Is Predictive of Platinum Response in Head and Neck Cancer Patients. Cancer Research 2015, 75: 1205-1215. PMID: 25691460, PMCID: PMC4615655, DOI: 10.1158/0008-5472.can-14-2729.Peer-Reviewed Original ResearchConceptsNeck cancer patientsEvolutionary action scoreCancer patientsTP53 mutationsNeck squamous cell carcinomaSquamous cell carcinomaCisplatin-based therapyPlatinum-based therapySubset of headThird of casesNovel scoring systemSurvival benefitProspective evaluationCell carcinomaPlatinum responsePreclinical modelsTreatment selectionAction scoresScoring systemPatientsHNSCCTherapyCoding variantPredictive responseScores
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