2021
Patterns of treatment with everolimus exemestane in hormone receptor-positive HER2-negative metastatic breast cancer in the era of targeted therapy
Rozenblit M, Mun S, Soulos P, Adelson K, Pusztai L, Mougalian S. Patterns of treatment with everolimus exemestane in hormone receptor-positive HER2-negative metastatic breast cancer in the era of targeted therapy. Breast Cancer Research 2021, 23: 14. PMID: 33514405, PMCID: PMC7844919, DOI: 10.1186/s13058-021-01394-y.Peer-Reviewed Original ResearchConceptsPrior endocrine therapyEndocrine therapyMetastatic breast cancerEffective treatment optionTreatment optionsBreast cancerMedian treatmentMedian OSEE therapyHormone receptor-positive HER2-negative metastatic breast cancerMultivariable Cox proportional hazards regression analysisHER2-negative metastatic breast cancerPrior treatmentCox proportional hazards regression analysisFirst-line therapy initiationProportional hazards regression analysisPrior treatment optionsLines of therapyProportion of patientsKaplan-Meier methodHazards regression analysisPatterns of treatmentElectronic health record-derived dataClinical trial dataOS benefit
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 developmentImmunotherapy and targeted therapy combinations in metastatic breast cancer
Esteva FJ, Hubbard-Lucey VM, Tang J, Pusztai L. Immunotherapy and targeted therapy combinations in metastatic breast cancer. The Lancet Oncology 2019, 20: e175-e186. PMID: 30842061, DOI: 10.1016/s1470-2045(19)30026-9.Peer-Reviewed Original ResearchConceptsMetastatic breast cancerBreast cancerImmune checkpoint inhibitorsTumor-infiltrating lymphocytesDeath ligand 1Most breast cancersNew treatment modalitiesSingle-drug therapyCyclin-dependent kinase 4Development of combinationsCheckpoint inhibitorsEndocrine therapyDeath-1Immunotherapeutic approachesBiological therapyTherapy combinationsTreatment modalitiesLittle efficacyImmune evasionAngiogenesis inhibitorsTherapyImmunotherapyCancerPolymerase inhibitorsMonoclonal antibodies
2018
TQuest, A Web-Based Platform to Enable Precision Medicine by Linking a Tumor’s Genetic Defects to Therapeutic Options
Gershkovich P, Platt J, Knopf J, Tasoulis MK, Shi W, Pusztai L, Hatzis C. TQuest, A Web-Based Platform to Enable Precision Medicine by Linking a Tumor’s Genetic Defects to Therapeutic Options. JCO Clinical Cancer Informatics 2018, 2: 1-13. PMID: 30652574, DOI: 10.1200/cci.17.00120.Peer-Reviewed Original ResearchConceptsData acquisition layerFull-text indexAcquisition layerUser interfaceData layersPrototype web applicationWeb-based platformWeb applicationRelevance scoresSearch enginesSource codeSoftware toolsSearch resultsInterventional clinical trialsLabel dataClinical trialsTherapeutic optionsPlatformUS FoodMolecular abnormalitiesMetastatic breast cancerPotential therapeutic optionPotential treatment optionTumor DNA sequencingWeb-based modulesA framework to rank genomic alterations as targets for cancer precision medicine: the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT)
Mateo J, Chakravarty D, Dienstmann R, Jezdic S, Gonzalez-Perez A, Lopez-Bigas N, Ng CKY, Bedard PL, Tortora G, Douillard J, Van Allen EM, Schultz N, Swanton C, André F, Pusztai L. A framework to rank genomic alterations as targets for cancer precision medicine: the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT). Annals Of Oncology 2018, 29: 1895-1902. PMID: 30137196, PMCID: PMC6158764, DOI: 10.1093/annonc/mdy263.Peer-Reviewed Original ResearchConceptsESMO ScaleMolecular targetsClinical actionabilityPrecision Medicine Working GroupGenomic alterationsPrecision medicineRoutine clinical decisionEvidence-based criteriaMedicine Working GroupLack of evidencePreclinical evidenceClinical benefitClinical evidencePatient populationClassification systemClinical managementCancer precision medicineInvestigational targetsPatient managementMolecular aberrationsTumor typesClinical decisionClinical targetsAvailable evidenceEuropean Society
2017
Pathway level alterations rather than mutations in single genes predict response to HER2-targeted therapies in the neo-ALTTO trial
Shi W, Jiang T, Nuciforo P, Hatzis C, Holmes E, Harbeck N, Sotiriou C, Peña L, Loi S, Rosa DD, Chia S, Wardley A, Ueno T, Rossari J, Eidtmann H, Armour A, Piccart-Gebhart M, Rimm DL, Baselga J, Pusztai L. Pathway level alterations rather than mutations in single genes predict response to HER2-targeted therapies in the neo-ALTTO trial. Annals Of Oncology 2017, 28: 128-135. PMID: 28177460, PMCID: PMC5834036, DOI: 10.1093/annonc/mdw434.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Combined Chemotherapy ProtocolsBiopsy, Fine-NeedleBreast NeoplasmsClass I Phosphatidylinositol 3-KinasesDNA, NeoplasmExome SequencingFemaleHumansLapatinibMolecular Targeted TherapyMutationProportional Hazards ModelsProtein Kinase InhibitorsQuinazolinesReceptor, ErbB-2RhoA GTP-Binding ProteinTrastuzumabConceptsPathologic complete response
2016
Is precision medicine ready for use in breast cancer?
Pusztai L. Is precision medicine ready for use in breast cancer? Clinical Advances In Hematology And Oncology 2016, 14: 964-966. PMID: 28212357.Peer-Reviewed Original ResearchAntineoplastic AgentsBreast NeoplasmsFemaleHumansMolecular Targeted TherapyPrecision MedicineTranscriptomeDeciphering and Targeting Oncogenic Mutations and Pathways in Breast Cancer
Santarpia L, Bottai G, Kelly CM, Győrffy B, Székely B, Pusztai L. Deciphering and Targeting Oncogenic Mutations and Pathways in Breast Cancer. The Oncologist 2016, 21: 1063-1078. PMID: 27384237, PMCID: PMC5016060, DOI: 10.1634/theoncologist.2015-0369.Peer-Reviewed Original ResearchConceptsBreast cancerCancer-causing genesCopy number variationsRNA speciesRNA editingGenomic variationNext-generation sequencingRNA sequencingGenomic complexityGenomic portraitGreater genomic complexityOncogenic mutationsOncogenic eventsTarget profilingRare mutationsMutationsRecurrent mutationsSomatic variantsGenetic aberrationsFormal clinical trialsPotential therapeutic implicationsDriver mutationsSequencingGermline variantsMolecular abnormalitiesMutation based treatment recommendations from next generation sequencing data: a comparison of web tools
Patel JM, Knopf J, Reiner E, Bossuyt V, Epstein L, DiGiovanna M, Chung G, Silber A, Sanft T, Hofstatter E, Mougalian S, Abu-Khalaf M, Platt J, Shi W, Gershkovich P, Hatzis C, Pusztai L. Mutation based treatment recommendations from next generation sequencing data: a comparison of web tools. Oncotarget 2016, 7: 22064-22076. PMID: 26980737, PMCID: PMC5008344, DOI: 10.18632/oncotarget.8017.Peer-Reviewed Original ResearchMeSH KeywordsBreast NeoplasmsDrug Therapy, Computer-AssistedFemaleHigh-Throughput Nucleotide SequencingHumansInternetMolecular Targeted TherapyPrecision MedicineSoftwareConceptsWeb toolArtificial intelligence toolsApplicable software toolsReal-time statusDifferent web toolsIntelligence toolsSoftware toolsRecommendation toolGeneration sequencing dataNext-generation sequencing dataData acquisitionInteraction databasesGenomic dataRecommendation sourcesCancer genome dataProfiling resultsToolDrug-gene interaction databaseMore sourcesGenome dataAlgorithmPlatformPersonalized cancer therapy
2014
Metabolic isoenzyme shifts in cancer as potential novel therapeutic targets
Ononye SN, Shi W, Wali VB, Aktas B, Jiang T, Hatzis C, Pusztai L. Metabolic isoenzyme shifts in cancer as potential novel therapeutic targets. Breast Cancer Research And Treatment 2014, 148: 477-488. PMID: 25395317, DOI: 10.1007/s10549-014-3194-1.Peer-Reviewed Original ResearchMeSH KeywordsDatabases, ProteinEnergy MetabolismEnzyme InhibitorsGene Expression Regulation, NeoplasticGlycolysisHumansIsoenzymesMetabolic Networks and PathwaysMolecular Targeted TherapyNeoplasmsConceptsIsoform-specific inhibitorsMetabolic isoenzymesCancer cellsNeoplastic transformationMetabolic enzyme expressionFunctional redundancyEnzymatic functionIsoenzyme diversityAdditional isoformsCancer metabolismMetabolic enzymesSingle isoformMetabolic pathwaysPotential novel therapeutic targetNovel therapeutic targetMetabolic precursorsEnzyme expressionNormal cellsNew therapeutic strategiesStages of developmentIsoformsTherapeutic targetExpressionIsoenzyme expressionTreatment of cancerA Targeted Next‐Generation Sequencing Assay Detects a High Frequency of Therapeutically Targetable Alterations in Primary and Metastatic Breast Cancers: Implications for Clinical Practice
Vasan N, Yelensky R, Wang K, Moulder S, Dzimitrowicz H, Avritscher R, Wang B, Wu Y, Cronin MT, Palmer G, Symmans WF, Miller VA, Stephens P, Pusztai L. A Targeted Next‐Generation Sequencing Assay Detects a High Frequency of Therapeutically Targetable Alterations in Primary and Metastatic Breast Cancers: Implications for Clinical Practice. The Oncologist 2014, 19: 453-458. PMID: 24710307, PMCID: PMC4012963, DOI: 10.1634/theoncologist.2013-0377.Peer-Reviewed Original ResearchConceptsBreast cancerGenomic alterationsV-akt murine thymoma viral oncogene homolog 1Stage IV cancerMetastatic breast cancerActionable genomic alterationsPotential treatment optionOncogene homolog 1Primary tumor biopsiesCancer-related genesClinical Laboratory Improvement AmendmentsDependent kinasesMedian sequencing depthGene fusionsSequencing depthBase substitutionsHER2 mutationsHomolog 1Actionable alterationsTargetable alterationsTreatment optionsClinical trialsHER2 amplificationMetastatic cancerTumor biopsies
2012
Mutation profiling identifies numerous rare drug targets and distinct mutation patterns in different clinical subtypes of breast cancers
Santarpia L, Qi Y, Stemke-Hale K, Wang B, Young EJ, Booser DJ, Holmes FA, O’Shaughnessy J, Hellerstedt B, Pippen J, Vidaurre T, Gomez H, Valero V, Hortobagyi GN, Symmans WF, Bottai G, Di Leo A, Gonzalez-Angulo AM, Pusztai L. Mutation profiling identifies numerous rare drug targets and distinct mutation patterns in different clinical subtypes of breast cancers. Breast Cancer Research And Treatment 2012, 134: 333-343. PMID: 22538770, PMCID: PMC3885980, DOI: 10.1007/s10549-012-2035-3.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerBreast cancer subtypesBreast cancerPIK3CA mutationsCancer subtypesEstrogen receptor-positive cancersBreast cancer molecular subtypesMajor breast cancer subtypesSingle needle biopsyProspective clinical trialsReceptor-positive cancersDifferent breast cancer subtypesDifferent clinical subtypesNegative breast cancerCancer molecular subtypesFine-needle aspirationMutation patternsClinical subtypesClinical trialsNeedle biopsyMolecular subtypesNeedle aspirationInvestigational drugsStage IFBXW7 mutations