2023
In Vivo and In Vitro Efficacy of Trastuzumab Deruxtecan in Uterine Serous Carcinoma.
Mutlu L, Manavella D, Bellone S, McNamara B, Harold J, Mauricio D, Siegel E, Buza N, Hui P, Hartwich T, Yang-Hartwich Y, Demirkiran C, Verzosa M, Altwerger G, Ratner E, Huang G, Clark M, Andikyan V, Azodi M, Dottino P, Schwartz P, Santin A. In Vivo and In Vitro Efficacy of Trastuzumab Deruxtecan in Uterine Serous Carcinoma. Molecular Cancer Therapeutics 2023, 22: 1404-1412. PMID: 37676984, DOI: 10.1158/1535-7163.mct-23-0126.Peer-Reviewed Original ResearchConceptsUterine serous carcinomaAntibody-dependent cellular cytotoxicityT-DXdUSC patientsUSC cell linesTrastuzumab deruxtecanSerous carcinomaHER2 expressionClinical trialsRecurrent uterine serous carcinomaTopoisomerase I inhibitor payloadSignificant antibody-dependent cellular cytotoxicityCell linesMultiple tumor indicationsPrimary USC cell linesLow HER2 expressionFuture clinical trialsHigh recurrence ratePeripheral blood lymphocytesERBB2 gene amplificationGrowth suppressionHER2-overexpressing cell linesTumor growth suppressionOverall survivalStandard chemotherapyMonitoring Treatment Response, Early Recurrence, and Survival in Uterine Serous Carcinoma and Carcinosarcoma Patients Using Personalized Circulating Tumor DNA Biomarkers
Bellone S, McNamara B, Mutlu L, Demirkiran C, Hartwich T, Harold J, Yang-Hartwich Y, Siegel E, Santin A. Monitoring Treatment Response, Early Recurrence, and Survival in Uterine Serous Carcinoma and Carcinosarcoma Patients Using Personalized Circulating Tumor DNA Biomarkers. International Journal Of Molecular Sciences 2023, 24: 8873. PMID: 37240216, PMCID: PMC10219151, DOI: 10.3390/ijms24108873.Peer-Reviewed Original ResearchConceptsUterine serous carcinomaCS patientsEarly recurrenceDroplet digital polymerase chain reactionCA 125Serous carcinomaCtDNA testingTime of surgeryTime of recurrenceReliable tumor biomarkersTumour DNA biomarkersCarcinosarcoma patientsUSC patientsRecurrent diseaseOccult diseaseOverall survivalEndometrial cancerAggressive variantInitial treatmentRecurrent tumorsResidual tumorClinical findingsTreatment courseTreatment trialsPIK3CA mutations
2022
Synergistic activity of neratinib in combination with olaparib in uterine serous carcinoma overexpressing HER2/neu
Yadav G, Roque DM, Bellone S, Manavella DD, Hartwich TMP, Zipponi M, Harold J, Tymon-Rosario J, Mutlu L, Altwerger G, Menderes G, Ratner E, Buza N, Hui P, Huang GS, Andikyan V, Clark M, Azodi M, Schwartz PE, Alexandrov LB, Santin AD. Synergistic activity of neratinib in combination with olaparib in uterine serous carcinoma overexpressing HER2/neu. Gynecologic Oncology 2022, 166: 351-357. PMID: 35641325, DOI: 10.1016/j.ygyno.2022.05.021.Peer-Reviewed Original ResearchConceptsUterine serous carcinomaHER2/neu expressionHER2/neuCombination of olaparibUSC xenograftsUSC cell linesNeu expressionSerous carcinomaLow HER2/neu expressionHER2/neu 3Cell linesHER2/neu gene amplificationNovel therapeutic optionsPolymerase inhibitor olaparibNeu gene amplificationDurable growth inhibitionNeratinib treatmentUSC cellsUSC patientsEndometrial cancerAggressive variantTherapeutic optionsPoor prognosisHER2/Single agent
2020
Stage III uterine serous carcinoma: modern trends in multimodality treatment
Li JY, Young MR, Huang G, Litkouhi B, Santin A, Schwartz PE, Damast S. Stage III uterine serous carcinoma: modern trends in multimodality treatment. Journal Of Gynecologic Oncology 2020, 31: e53. PMID: 32266802, PMCID: PMC7286763, DOI: 10.3802/jgo.2020.31.e53.Peer-Reviewed Original ResearchConceptsUterine serous carcinomaExternal beam RTVaginal brachytherapyOverall survivalHuman epidermal growth factor receptorModern treatment eraSentinel node samplingRegional nodal recurrenceKaplan-Meier estimatesLog-rank testCox proportional hazardsExternal beam radiotherapyEpidermal growth factor receptorERA treatmentGrowth factor receptorUSC patientsFree survivalNodal recurrenceTreatment eraMultimodality treatmentPatient characteristicsPerioperative periodRegional nodalSerous carcinomaNode samplingSelection of HER2/NEU negative tumor cells as a mechanism of resistance to trastuzumab in uterine serous carcinoma
Pelligra S, Buza N, Hui P, Bellone S, Zeybek B, Ratner E, Schwartz PE, Scambia G, Santin AD. Selection of HER2/NEU negative tumor cells as a mechanism of resistance to trastuzumab in uterine serous carcinoma. Gynecologic Oncology Reports 2020, 32: 100554. PMID: 32140533, PMCID: PMC7049633, DOI: 10.1016/j.gore.2020.100554.Peer-Reviewed Original ResearchUterine serous carcinomaHER2/neuNegative tumor cellsUSC patientsTumor cellsSerous carcinomaHER2/neu overexpressionCarboplatin/paclitaxelInitial clinical responsePost-treatment biopsiesHumanized monoclonal antibodyC-erbB2 gene amplificationNCCN guidelinesClinical responseEndometrial cancerPreferred regimenAggressive variantMechanisms of resistanceNeu overexpressionRecurrent/HER2/TrastuzumabPatientsMonoclonal antibodiesNeu
2019
In vitro and in vivo activity of sacituzumab govitecan, an antibody-drug conjugate targeting trophoblast cell-surface antigen 2 (Trop-2) in uterine serous carcinoma
Han C, Perrone E, Zeybek B, Bellone S, Tymon-Rosario J, Altwerger G, Menderes G, Feinberg J, Haines K, Muller Karger ME, Bianchi A, Zammataro L, Manzano A, Bonazzoli E, Manara P, Buza N, Hui P, Ratner E, Silasi DA, Huang GS, Azodi M, Schwartz PE, Lopez S, Santin AD. In vitro and in vivo activity of sacituzumab govitecan, an antibody-drug conjugate targeting trophoblast cell-surface antigen 2 (Trop-2) in uterine serous carcinoma. Gynecologic Oncology 2019, 156: 430-438. PMID: 31839338, DOI: 10.1016/j.ygyno.2019.11.018.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, Monoclonal, HumanizedAntibody-Dependent Cell CytotoxicityAntigens, NeoplasmCamptothecinCell Adhesion MoleculesCell Line, TumorCystadenocarcinoma, SerousFemaleFlow CytometryHumansImmunoconjugatesImmunohistochemistryMiceMice, SCIDMolecular Targeted TherapyRandom AllocationTissue Array AnalysisUterine NeoplasmsXenograft Model Antitumor AssaysConceptsUterine serous carcinomaCell surface antigen 2Sacituzumab govitecanTrop-2 expressionTrop-2Serous carcinomaAntigen 2Advanced/recurrent diseasePrimary uterine serous carcinomaResistant human tumorsSignificant bystander killingUSC patientsUSC xenograftsRecurrent diseaseClinical responseEndometrial cancerAggressive variantPoor prognosisPreclinical activityPrimary tumorIntravenous administrationClinical developmentUSC samplesActive metaboliteSN-38
2018
Mechanisms of resistance to HER2-targeted therapies in HER2-amplified uterine serous carcinoma, and strategies to overcome it.
Menderes G, Lopez S, Han C, Altwerger G, Gysler S, Varughese J, Schwartz PE, Santin AD. Mechanisms of resistance to HER2-targeted therapies in HER2-amplified uterine serous carcinoma, and strategies to overcome it. Discovery Medicine 2018, 26: 39-50. PMID: 30265854.Peer-Reviewed Original ResearchConceptsUterine serous carcinomaTyrosine kinase inhibitorsUSC patientsSerous carcinomaHER2/neu-targeted therapiesEndometrial cancer-related deathsHER2/neu amplificationKinase inhibitorsSingle-agent trastuzumabSignificant clinical activityRecent whole-exome sequencing studiesCancer-related deathEffective therapeutic strategyTumor growth inhibitionEndometrial cancerAggressive subtypeMechanisms of resistanceWhole-exome sequencing studiesClinical activityPreclinical studiesTarget therapyTherapeutic strategiesNeu amplificationHER2TherapySacituzumab Govitecan (IMMU-132) in treatment-resistant uterine serous carcinoma: A case report
Han C, Bellone S, Schwartz PE, Govindan SV, Sharkey RM, Goldenberg DM, Santin AD. Sacituzumab Govitecan (IMMU-132) in treatment-resistant uterine serous carcinoma: A case report. Gynecologic Oncology Reports 2018, 25: 37-40. PMID: 29977989, PMCID: PMC6030029, DOI: 10.1016/j.gore.2018.05.009.Peer-Reviewed Original ResearchUterine serous carcinomaSacituzumab govitecanAntibody-drug conjugatesSerous carcinomaTreatment optionsNovel antibody-drug conjugateTreatment-resistant diseaseImpressive clinical responsesSignificant adverse eventsEffective treatment optionNew treatment optionsSerial CT scansUSC patientsAdverse eventsClinical responseMultiple chemotherapyAggressive variantCase reportUterine cancerClinical trialsCT scanDramatic responseSurface antigenTrop-2ChemotherapyIn vitro and in vivo activity of IMGN853, an Antibody-Drug Conjugate targeting Folate Receptor Alpha linked to DM4, in biologically aggressive endometrial cancers
Altwerger G, Bonazzoli E, Bellone S, Egawa-Takata T, Menderes G, Pettinella F, Bianchi A, Riccio F, Feinberg J, Zammataro L, Han C, Yadav G, Dugan K, Morneault A, Ponte JF, Buza N, Hui P, Wong S, Litkouhi B, Ratner E, Silasi DA, Huang GS, Azodi M, Schwartz PE, Santin AD. In vitro and in vivo activity of IMGN853, an Antibody-Drug Conjugate targeting Folate Receptor Alpha linked to DM4, in biologically aggressive endometrial cancers. Molecular Cancer Therapeutics 2018, 17: molcanther.0930.2017. PMID: 29440294, PMCID: PMC5932245, DOI: 10.1158/1535-7163.mct-17-0930.Peer-Reviewed Original ResearchConceptsEndometrial cancerXenograft modelCell linesTumor cell linesPatient-derived xenograft modelsUterine cancer cell linesAggressive endometrial cancersEndometrial cancer deathsExpression of FRαPrimary USC cell linesRecurrent endometrial cancerReceptor alpha expressionUSC cell linesImpressive antitumor activityMol Cancer TherUSC patientsCancer cell linesMedian survivalCancer deathPDX modelsPreclinical dataUterine cancerComplete resolutionIMGN853Grade 3
2016
Regression of metastatic, radiation/chemotherapy-resistant uterine serous carcinoma overexpressing HER2/neu with trastuzumab emtansine (TDM-1)
Santin AD, Bellone S, Buza N, Schwartz PE. Regression of metastatic, radiation/chemotherapy-resistant uterine serous carcinoma overexpressing HER2/neu with trastuzumab emtansine (TDM-1). Gynecologic Oncology Reports 2016, 19: 10-12. PMID: 28018954, PMCID: PMC5175991, DOI: 10.1016/j.gore.2016.12.003.Peer-Reviewed Original ResearchTDM-1Remarkable clinical responsesAlternative therapeutic optionUterine serous carcinomaNovel treatment optionsAbdominal wall musclesUSC patientsClinical responseTumor depositsSerous carcinomaTherapeutic optionsTreatment optionsTrastuzumab emtansineComplete resolutionCAT scanSystemic controlWall musclesPatientsCarcinomaHER2NeuChemotherapyEmtansineSurgeryOptionsDual CCNE1/PIK3CA targeting is synergistic in CCNE1-amplified/PIK3CA-mutated uterine serous carcinomas in vitro and in vivo
Cocco E, Lopez S, Black J, Bellone S, Bonazzoli E, Predolini F, Ferrari F, Schwab CL, Menderes G, Zammataro L, Buza N, Hui P, Wong S, Zhao S, Bai Y, Rimm DL, Ratner E, Litkouhi B, Silasi DA, Azodi M, Schwartz PE, Santin AD. Dual CCNE1/PIK3CA targeting is synergistic in CCNE1-amplified/PIK3CA-mutated uterine serous carcinomas in vitro and in vivo. British Journal Of Cancer 2016, 115: 303-311. PMID: 27351214, PMCID: PMC4973158, DOI: 10.1038/bjc.2016.198.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsCell Line, TumorClass I Phosphatidylinositol 3-KinasesCyclin EDNA Copy Number VariationsFemaleGene Knockdown TechniquesHeterograftsHumansIn Situ Hybridization, FluorescenceIn Vitro TechniquesMiceMutationOncogene ProteinsPhosphatidylinositol 3-KinasesRNA, MessengerTissue Array AnalysisUterine NeoplasmsConceptsUterine serous carcinomaSerous carcinomaTumor growthCyclin E1 (CCNE1) gene amplificationRecurrent uterine serous carcinomaPrimary USC cell linesNovel therapeutic optionsSingle-agent treatmentIdeal therapeutic targetUSC cell linesCyclin E1 expressionUSC patientsUSC xenograftsInhibited cell growthCell cycle analysisAggressive variantTherapeutic optionsCCNE1 amplificationEndometrial tumorsCYC065Therapeutic targetClinical optionPIK3CA driver mutationsDriver mutationsXenografts
2015
Dual HER2/PIK3CA Targeting Overcomes Single-Agent Acquired Resistance in HER2-Amplified Uterine Serous Carcinoma Cell Lines In Vitro and In Vivo
Lopez S, Cocco E, Black J, Bellone S, Bonazzoli E, Predolini F, Ferrari F, Schwab CL, English DP, Ratner E, Silasi DA, Azodi M, Schwartz PE, Terranova C, Angioli R, Santin AD. Dual HER2/PIK3CA Targeting Overcomes Single-Agent Acquired Resistance in HER2-Amplified Uterine Serous Carcinoma Cell Lines In Vitro and In Vivo. Molecular Cancer Therapeutics 2015, 14: 2519-2526. PMID: 26333383, PMCID: PMC4636465, DOI: 10.1158/1535-7163.mct-15-0383.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic Combined Chemotherapy ProtocolsCell CycleCell Line, TumorCell SurvivalClass I Phosphatidylinositol 3-KinasesCystadenocarcinoma, SerousDose-Response Relationship, DrugDrug SynergismFemaleGene AmplificationHumansImidazolesImmunoblottingMice, SCIDMutationOxazepinesPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsPhosphorylationQuinolinesReceptor, ErbB-2Uterine NeoplasmsXenograft Model Antitumor AssaysConceptsHER2/neu gene amplificationNeu gene amplificationUSC xenograftsUterine serous carcinomaGene amplificationUterine serous carcinoma cell linesSingle-agent therapyNovel therapeutic optionsWild-type PIK3CADose-dependent increaseIdeal therapeutic targetUSC cell linesCell linesDose-dependent declineFlow cytometry assayG0-G1 phaseCell cycle distributionOncogenic PIK3CA mutationsPercentage of cellsUSC patientsEndometrial cancerAggressive variantSerous carcinomaTherapeutic optionsCarcinoma cell lines
2014
T‐DM1, a novel antibody–drug conjugate, is highly effective against primary HER2 overexpressing uterine serous carcinoma in vitro and in vivo
English DP, Bellone S, Schwab CL, Bortolomai I, Bonazzoli E, Cocco E, Buza N, Hui P, Lopez S, Ratner E, Silasi D, Azodi M, Schwartz PE, Rutherford TJ, Santin AD. T‐DM1, a novel antibody–drug conjugate, is highly effective against primary HER2 overexpressing uterine serous carcinoma in vitro and in vivo. Cancer Medicine 2014, 3: 1256-1265. PMID: 24890382, PMCID: PMC4302675, DOI: 10.1002/cam4.274.Peer-Reviewed Original ResearchMeSH KeywordsAdo-Trastuzumab EmtansineAgedAged, 80 and overAnimalsAntibodies, Monoclonal, HumanizedAntibody-Dependent Cell CytotoxicityAntineoplastic AgentsApoptosisCarcinomaCell Cycle CheckpointsCell ProliferationDisease Models, AnimalFemaleGene AmplificationGene ExpressionGene Expression Regulation, NeoplasticHumansImmunohistochemistryIn Situ Hybridization, FluorescenceMaytansineMiddle AgedReceptor, ErbB-2RNA, MessengerTrastuzumabUterine NeoplasmsXenograft Model Antitumor AssaysConceptsUterine serous carcinomaUSC cell linesNovel antibody-drug conjugateT-DM1USC xenograftsAntibody-drug conjugatesSerous carcinomaAntibody-dependent cell-mediated cytotoxicityEpidermal growth factor receptor 2Cell linesPrimary USC cell linesGrowth factor receptor 2Cell-mediated cytotoxicityChromium release assaysNovel treatment optionsHER2 protein overexpressionFactor receptor 2HER2 gene amplificationHER2 protein expressionC-erbB2 gene amplificationGene amplificationDisease refractoryPrimary HER2USC cellsUSC patients
2013
HER2/neu gene amplification determines the sensitivity of uterine serous carcinoma cell lines to AZD8055, a novel dual mTORC1/2 inhibitor
English DP, Roque DM, Carrara L, Lopez S, Bellone S, Cocco E, Bortolomai I, Schwartz PE, Rutherford T, Santin AD. HER2/neu gene amplification determines the sensitivity of uterine serous carcinoma cell lines to AZD8055, a novel dual mTORC1/2 inhibitor. Gynecologic Oncology 2013, 131: 753-758. PMID: 24012800, DOI: 10.1016/j.ygyno.2013.08.033.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic AgentsCarcinoma, PapillaryCell Line, TumorCystadenocarcinoma, SerousFemaleGene AmplificationHumansMechanistic Target of Rapamycin Complex 1Mechanistic Target of Rapamycin Complex 2MorpholinesMultiprotein ComplexesProtein Kinase InhibitorsReceptor, ErbB-2TOR Serine-Threonine KinasesUterine NeoplasmsConceptsUSC cell linesC-erbB2 gene amplificationUterine serous carcinoma cell linesDual mTORC1/2 inhibitorCarcinoma cell linesC-erbB2Cell linesGene amplificationMTORC1/2 inhibitorsPrimary USC cell linesHER2/neu gene amplificationG0/G1 cell cycle phaseDose-dependent increaseHigh HER-2HER2/neuNeu gene amplificationDose-dependent declinePercentage of cellsUSC patientsHER-2Cell cycle profileDifferential growth inhibitionG1 cell cycle phasePS6 levelsTherapeutic agents
2012
Prognostic factors and treatment-related outcomes in patients with uterine serous cancer (USC).
deLeon M, Lu L, Hui P, Santin A, Rutherford T, Arin-Silasi D, Azodi M, Ratner E, Schwartz P. Prognostic factors and treatment-related outcomes in patients with uterine serous cancer (USC). Journal Of Clinical Oncology 2012, 30: 5099-5099. DOI: 10.1200/jco.2012.30.15_suppl.5099.Peer-Reviewed Original ResearchStage IA/IBDisease-free survivalUterine serous cancerIIIA/IIIBIVA/IVBIA/IBUSC patientsPrognostic factorsMyometrial invasionLargest single-institution experienceWhole-pelvis radiation therapyLymph node involvementPlatinum-based chemotherapySingle institution experienceIndependent prognostic factorLymph node metastasisTreatment-related outcomesUterine cancer deathsBetter OSII-IVBIB diseaseNode involvementSurgical debulkingSerous cancerShorter OSDemographics of uterine serous cancer (USC) patients: A single institutional experience.
de Leon M, Lu L, Hui P, Santin A, Rutherford T, Arin-Silasi D, Azodi M, Ratner E, Schwartz P. Demographics of uterine serous cancer (USC) patients: A single institutional experience. Journal Of Clinical Oncology 2012, 30: e15581-e15581. DOI: 10.1200/jco.2012.30.15_suppl.e15581.Peer-Reviewed Original ResearchPast medical historyUterine cancerUSC patientsSEER dataBreast cancerPrior historyLargest single-institution experienceCommon uterine cancerSerous cancer patientsSmall institutional seriesSingle institution experienceSingle institutional experienceForms of cancerOlder ptsPt ageDiabetic womenPostmenopausal womenFIGO stageInstitutional seriesOral contraceptivesMenopause statusCancer patientsDisease stageMedical historyEstrogen dependency
2011
Her2/neu extracellular domain shedding in uterine serous carcinoma: implications for immunotherapy with trastuzumab
Todeschini P, Cocco E, Bellone S, Varughese J, Lin K, Carrara L, Guzzo F, Buza N, Hui P, Silasi DA, Ratner E, Azodi M, Schwartz PE, Rutherford TJ, Pecorelli S, Santin AD. Her2/neu extracellular domain shedding in uterine serous carcinoma: implications for immunotherapy with trastuzumab. British Journal Of Cancer 2011, 105: 1176-1182. PMID: 21915118, PMCID: PMC3208497, DOI: 10.1038/bjc.2011.369.Peer-Reviewed Original ResearchMeSH KeywordsAgedAged, 80 and overAntibodies, Monoclonal, HumanizedAntibody-Dependent Cell CytotoxicityAntineoplastic AgentsCulture Media, ConditionedFemaleFlow CytometryGenes, erbB-2HumansImmunohistochemistryImmunotherapyIn Situ Hybridization, FluorescenceMiddle AgedReal-Time Polymerase Chain ReactionTrastuzumabUterine NeoplasmsConceptsAntibody-dependent cell-mediated cytotoxicityTrastuzumab-mediated antibody-dependent cell-mediated cytotoxicityUSC cell linesHER2/neu expressionUSC patientsNeu expressionHER2/ECD levelsCell linesUterine serous carcinoma cell linesCell-mediated cytotoxicityUterine serous carcinomaChromium release assaysHER2/neuFISH-positive tumorsC-erbB2 gene amplificationTrastuzumab-induced cytotoxicityNeu tumorsHealthy womenSerous carcinomaCarcinoma cell linesReal-time PCRTherapeutic effectC-erbB2 genePatients