2023
Pan-cancer analysis of antibody-drug conjugate targets and putative predictors of treatment response
Bosi C, Bartha Á, Galbardi B, Notini G, Naldini M, Licata L, Viale G, Mariani M, Pistilli B, Ali H, André F, Piras M, Callari M, Barreca M, Locatelli A, Viganò L, Criscitiello C, Pusztai L, Curigliano G, Győrffy B, Dugo M, Bianchini G. Pan-cancer analysis of antibody-drug conjugate targets and putative predictors of treatment response. European Journal Of Cancer 2023, 195: 113379. PMID: 37913680, DOI: 10.1016/j.ejca.2023.113379.Peer-Reviewed Original ResearchConceptsGenotype-Tissue Expression (GTEx) databaseAntibody-drug conjugatesADC targetPan-cancer analysisCancer Genome AtlasExpression distributionGene expressionNew therapeutic opportunitiesTreatment responseExpression of determinantsPrimary tissuesGenome AtlasExpression levelsNormal tissuesPotential downstreamProtein expressionRelative expressionExpression databaseGenesTherapeutic opportunitiesExpressionTarget expressionMRNA levelsCancer typesInter-patient heterogeneityMore than bad luck: Cancer and aging are linked to replication-driven changes to the epigenome
Minteer C, Thrush K, Gonzalez J, Niimi P, Rozenblit M, Rozowsky J, Liu J, Frank M, McCabe T, Sehgal R, Higgins-Chen A, Hofstatter E, Pusztai L, Beckman K, Gerstein M, Levine M. More than bad luck: Cancer and aging are linked to replication-driven changes to the epigenome. Science Advances 2023, 9: eadf4163. PMID: 37467337, PMCID: PMC10355820, DOI: 10.1126/sciadv.adf4163.Peer-Reviewed Original ResearchConceptsStem cell divisionImmortalized human cellsTissue-specific cancer riskTumorigenic stateCell divisionDNA methylationEpigenetic changesAge-related accumulationHuman cellsMultiple tissuesSomatic mutationsClinical tissuesTissue differencesEpigenomeCellsTissueNormal tissuesMethylationMutationsReplicationNormal breast tissueSignaturesVitroAccumulationDivision
2022
Comprehensive Analysis of Metabolic Isozyme Targets in Cancer
Marczyk M, Gunasekharan V, Casadevall D, Qing T, Foldi J, Sehgal R, Shan NL, Blenman KRM, O'Meara TA, Umlauf S, Surovtseva YV, Muthusamy V, Rinehart J, Perry RJ, Kibbey R, Hatzis C, Pusztai L. Comprehensive Analysis of Metabolic Isozyme Targets in Cancer. Cancer Research 2022, 82: 1698-1711. PMID: 35247885, PMCID: PMC10883296, DOI: 10.1158/0008-5472.can-21-3983.Peer-Reviewed Original ResearchConceptsPotential therapeutic targetAcetyl-CoA carboxylase 1Therapeutic targetCancer typesCell linesBreast cancer viabilityPatient-derived xenograftsNovel metabolic targetsCorresponding cell linesExpression patternsDrug treatmentMatching normal tissuesRelated commentaryTumor growthMalignant transformationSmall molecule inhibitionCancer viabilityCancer Cell Line EncyclopediaNormal tissuesMetabolic vulnerabilitiesCarboxylase 1Anticancer therapyCellular changesCell proliferationMetabolic reprogramming
2019
Identification and Validation of a Novel Biologics Target in Triple Negative Breast Cancer
Wali VB, Patwardhan GA, Pelekanou V, Karn T, Cao J, Ocana A, Yan Q, Nelson B, Hatzis C, Pusztai L. Identification and Validation of a Novel Biologics Target in Triple Negative Breast Cancer. Scientific Reports 2019, 9: 14934. PMID: 31624295, PMCID: PMC6797726, DOI: 10.1038/s41598-019-51453-w.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsBreastCell Line, TumorCell MembraneCell ProliferationDatasets as TopicDrug DevelopmentFemaleGABA-A Receptor AntagonistsGene Expression ProfilingGene Knockdown TechniquesHumansImmunoconjugatesImmunoglobulin Fab FragmentsMaytansineMiceMolecular Targeted TherapyReceptors, GABA-ATriple Negative Breast NeoplasmsXenograft Model Antitumor AssaysConceptsTriple-negative breast cancerNegative breast cancerTNBC cell growthBreast cancerMDA-MB-468 xenograftsPotential novel therapeutic targetNovel biologic targetsNovel therapeutic targetBreast cancer tissuesReceptors/cellAntibody-drug conjugate (ADC) developmentMost normal tissuesTreatment optionsCell growthTherapeutic targetBiologic targetsNude miceCancer tissuesVivo functional assaysLow expressionNormal tissuesNovel targetCancerSignificant anticancer activityADC development
2013
Genomic alterations in matching primary tumors and metastasis in breast cancer.
Jiang T, Szekely B, Szasz A, Kluger Y, Kulka J, Pusztai L. Genomic alterations in matching primary tumors and metastasis in breast cancer. Journal Of Clinical Oncology 2013, 31: 1549-1549. DOI: 10.1200/jco.2013.31.15_suppl.1549.Peer-Reviewed Original ResearchPrimary tumorPrimary cancerBreast cancerMetastatic lesionsDisease historyExtensive prior therapyPrimary breast cancerLonger disease historyWhole-exome sequencingDifferent tumor sitesFunctional impactPrior therapyNucleotide variantsMetastasisPatientsTumor siteTumorsCancerNormal tissuesCancer samplesExome sequencingGenomic alterationsLesionsMore mutationsExon Kit
2003
Jun activation domain binding protein 1 expression is associated with low p27(Kip1)levels in node-negative breast cancer.
Esteva FJ, Sahin AA, Rassidakis GZ, Yuan LX, Smith TL, Yang Y, Gilcrease MZ, Cristofanilli M, Nahta R, Pusztai L, Claret FX. Jun activation domain binding protein 1 expression is associated with low p27(Kip1)levels in node-negative breast cancer. Clinical Cancer Research 2003, 9: 5652-9. PMID: 14654548.Peer-Reviewed Original ResearchMeSH KeywordsBreast NeoplasmsCell Cycle ProteinsCOP9 Signalosome ComplexCyclin-Dependent Kinase Inhibitor p27DNA-Binding ProteinsFemaleGene Expression Regulation, NeoplasticGenes, Tumor SuppressorHumansImmunohistochemistryIntracellular Signaling Peptides and ProteinsLymphatic MetastasisMiddle AgedPeptide HydrolasesReceptor, ErbB-2Receptors, EstrogenSurvival AnalysisTime FactorsTranscription FactorsTumor Suppressor ProteinsConceptsNode-negative breast cancerAdjacent normal tissuesInvasive breast carcinomaBreast cancerJab1 overexpressionNormal tissuesBreast carcinomaAdjuvant systemic therapyDisease-free survivalIndependent prognostic factorInvasive breast cancerLow nuclear gradeBreast cancer tissuesExpression levelsProtein-1 expressionBreast tumor tissuesWestern blot analysisDomain-binding protein 1Patient agePrognostic factorsSystemic therapyPrognostic significanceTumor sizeNuclear gradeInvasive tumors
1998
Coexpression of the HER-2 Gene Product, pl85HER-2, and Epidermal Growth Factor Receptor, pl70EGF-R, on Epithelial Ovarian Cancers and Normal Tissues
Bast R, Pusztai L, Kerns B, MacDonald J, Jordan P, Daly L, Boyer C, Mendelsohn J, Berchuck A. Coexpression of the HER-2 Gene Product, pl85HER-2, and Epidermal Growth Factor Receptor, pl70EGF-R, on Epithelial Ovarian Cancers and Normal Tissues. Monoclonal Antibodies In Immunodiagnosis And Immunotherapy 1998, 17: 313-321. PMID: 9790065, DOI: 10.1089/hyb.1998.17.313.Peer-Reviewed Original ResearchConceptsOvarian cancerNormal ovarian epitheliumNormal tissuesOvarian epitheliumTumor cellsAdvanced ovarian cancerEpithelial ovarian cancerFavorable therapeutic indexCombination of antibodiesEpidermal growth factor receptorGrowth factor receptorEpithelial specimensHER-2Normal ovariesP170 expressionP185 expressionTherapeutic indexNeoplastic cellsTumor growthSynergistic cytotoxicityFrozen sectionsCancerTherapeutic activityDifferent antigensMonoclonal antibodies