2019
Selective inhibition of N-linked glycosylation impairs receptor tyrosine kinase processing
Klaver E, Zhao P, May M, Flanagan-Steet H, Freeze HH, Gilmore R, Wells L, Contessa J, Steet R. Selective inhibition of N-linked glycosylation impairs receptor tyrosine kinase processing. Disease Models & Mechanisms 2019, 12: dmm039602. PMID: 31101650, PMCID: PMC6602306, DOI: 10.1242/dmm.039602.Peer-Reviewed Original ResearchConceptsNull cellsReceptor processingEndoplasmic reticulum localizationGlycan site occupancyInsulin-like growth factor 1 receptorReceptor tyrosine kinasesGrowth factor 1 receptorFactor 1 receptorCell surface glycoproteinMutant cellsNGI-1Catalytic subunitReceptor kinaseGlycosylation statusReduced abundanceTyrosine kinaseGlycan occupancyTyrosine receptor kinaseSurface localizationInsulin receptorAbnormal glycosylationProteolytic processingFunctional consequencesCell surfaceGlycosylation
2017
Estimating Survival in Patients With Lung Cancer and Brain Metastases: An Update of the Graded Prognostic Assessment for Lung Cancer Using Molecular Markers (Lung-molGPA)
Sperduto PW, Yang TJ, Beal K, Pan H, Brown PD, Bangdiwala A, Shanley R, Yeh N, Gaspar LE, Braunstein S, Sneed P, Boyle J, Kirkpatrick JP, Mak KS, Shih HA, Engelman A, Roberge D, Arvold ND, Alexander B, Awad MM, Contessa J, Chiang V, Hardie J, Ma D, Lou E, Sperduto W, Mehta MP. Estimating Survival in Patients With Lung Cancer and Brain Metastases: An Update of the Graded Prognostic Assessment for Lung Cancer Using Molecular Markers (Lung-molGPA). JAMA Oncology 2017, 3: 827-831. PMID: 27892978, PMCID: PMC5824323, DOI: 10.1001/jamaoncol.2016.3834.Peer-Reviewed Original ResearchConceptsDiagnosis-Specific Graded Prognostic AssessmentBrain metastasesGraded Prognostic AssessmentFuture clinical trialsLung cancerLung-molGPAMedian survivalPrognostic factorsHazard ratioClinical trialsMAIN OUTCOMEPrognostic assessmentLung-molGPA scoreOverall median survivalKarnofsky performance statusMultiple Cox regressionSignificant prognostic factorsCell lung cancerRetrospective database analysisCancer-related mortalityLog-rank testHeterogeneous patient populationClinical decision makingExtracranial metastasesOverall survival
2016
Oligosaccharyltransferase inhibition induces senescence in RTK-driven tumor cells
Lopez-Sambrooks C, Shrimal S, Khodier C, Flaherty DP, Rinis N, Charest JC, Gao N, Zhao P, Wells L, Lewis TA, Lehrman MA, Gilmore R, Golden JE, Contessa JN. Oligosaccharyltransferase inhibition induces senescence in RTK-driven tumor cells. Nature Chemical Biology 2016, 12: 1023-1030. PMID: 27694802, PMCID: PMC5393272, DOI: 10.1038/nchembio.2194.Peer-Reviewed Original ResearchMeSH KeywordsBenzamidesCell Cycle CheckpointsCell Line, TumorCell ProliferationCellular SenescenceDose-Response Relationship, DrugEnzyme InhibitorsHexosyltransferasesHigh-Throughput Screening AssaysHumansMembrane ProteinsMolecular StructureReceptor Protein-Tyrosine KinasesStructure-Activity RelationshipSulfonamidesThe Effect of Gene Alterations and Tyrosine Kinase Inhibition on Survival and Cause of Death in Patients With Adenocarcinoma of the Lung and Brain Metastases
Sperduto PW, Yang TJ, Beal K, Pan H, Brown PD, Bangdiwala A, Shanley R, Yeh N, Gaspar LE, Braunstein S, Sneed P, Boyle J, Kirkpatrick JP, Mak KS, Shih HA, Engelman A, Roberge D, Arvold ND, Alexander B, Awad MM, Contessa J, Chiang V, Hardie J, Ma D, Lou E, Sperduto W, Mehta MP. The Effect of Gene Alterations and Tyrosine Kinase Inhibition on Survival and Cause of Death in Patients With Adenocarcinoma of the Lung and Brain Metastases. International Journal Of Radiation Oncology • Biology • Physics 2016, 96: 406-413. PMID: 27598807, PMCID: PMC5575932, DOI: 10.1016/j.ijrobp.2016.06.006.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAgedAged, 80 and overAnaplastic Lymphoma KinaseAntineoplastic AgentsBrain NeoplasmsErbB ReceptorsFemaleGenetic MarkersGenetic Predisposition to DiseaseHumansIncidenceLung NeoplasmsMaleMiddle AgedMutationPolymorphism, Single NucleotidePrevalenceProtein-Tyrosine KinasesReceptor Protein-Tyrosine KinasesRetrospective StudiesRisk FactorsSurvival RateUnited StatesConceptsTyrosine kinase inhibitionBrain metastasesMedian survivalCause of deathGene alterationsDiagnosis of BMMulti-institutional retrospective databaseTKI-naïve patientsRisk of deathLonger median survivalKinase inhibitionALK gene alterationsTreatment patternsCancer mortalityLung cancerPrimary diagnosisRetrospective databaseCommon causeLung adenocarcinomaGroup overallPatientsFirst treatmentPrior trialsEGFRMonths
2015
Extended Survival and Prognostic Factors for Patients With ALK-Rearranged Non–Small-Cell Lung Cancer and Brain Metastasis
Johung KL, Yeh N, Desai NB, Williams TM, Lautenschlaeger T, Arvold ND, Ning MS, Attia A, Lovly CM, Goldberg S, Beal K, Yu JB, Kavanagh BD, Chiang VL, Camidge DR, Contessa JN. Extended Survival and Prognostic Factors for Patients With ALK-Rearranged Non–Small-Cell Lung Cancer and Brain Metastasis. Journal Of Clinical Oncology 2015, 34: 123-129. PMID: 26438117, PMCID: PMC5070549, DOI: 10.1200/jco.2015.62.0138.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAnaplastic Lymphoma KinaseAntineoplastic AgentsBrain NeoplasmsCarbazolesCarcinoma, Non-Small-Cell LungCranial IrradiationCrizotinibDisease-Free SurvivalFemaleFollow-Up StudiesGene RearrangementHumansKaplan-Meier EstimateKarnofsky Performance StatusLung NeoplasmsMaleMiddle AgedMolecular Targeted TherapyNeoplasm StagingPiperidinesPrognosisProtein Kinase InhibitorsProtein-Tyrosine KinasesPyrazolesPyridinesPyrimidinesRadiosurgeryReceptor Protein-Tyrosine KinasesRisk AssessmentRisk FactorsSmokingSulfonesConceptsIntracranial progression-free survivalBrain metastasesProgression-free survivalPrognostic factorsLung cancerMedian intracranial progression-free survivalNon-small cell lung cancerTyrosine kinase inhibitor therapyProgressive brain metastasesRefinement of prognosisKarnofsky performance scorePercent of patientsClinical prognostic factorsPopulation of patientsSingle brain metastasisCell lung cancerKinase inhibitor therapyCox proportional hazardsMulti-institutional studyMedian OSExtracranial metastasesImproved survivalInhibitor therapyInitial treatmentMultivariable analysis
2013
A Clinical Model for Identifying Radiosensitive Tumor Genotypes in Non–Small Cell Lung Cancer
Johung KL, Yao X, Li F, Yu JB, Gettinger SN, Goldberg S, Decker RH, Hess JA, Chiang VL, Contessa JN. A Clinical Model for Identifying Radiosensitive Tumor Genotypes in Non–Small Cell Lung Cancer. Clinical Cancer Research 2013, 19: 5523-5532. PMID: 23897899, DOI: 10.1158/1078-0432.ccr-13-0836.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAnaplastic Lymphoma KinaseAntineoplastic AgentsBrain NeoplasmsCarcinoma, Non-Small-Cell LungErbB ReceptorsFemaleGenotypeHumansLung NeoplasmsMaleMiddle AgedMutationProtein Kinase InhibitorsRadiation ToleranceReceptor Protein-Tyrosine KinasesRecurrenceTranslocation, GeneticTumor BurdenConceptsNon-small cell lung cancerCell lung cancerEML4-ALK translocationGamma knife treatmentLocal controlTumor genotypeLung cancerEGFR mutationsCox proportional hazards modelDistant brain controlDistant brain recurrenceGamma knife radiotherapyEGFR kinase domain mutationsSuperior local controlField local controlKRAS mutation statusProportional hazards modelKinase domain mutationsEGF receptorMetastasis sizeBrain recurrenceBrain metastasesField recurrenceClinical outcomesIndependent predictors