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 ResearchMeSH KeywordsAntibodies, Monoclonal, HumanizedCamptothecinCarcinomaFemaleHumansImmunoconjugatesReceptor, ErbB-2TrastuzumabUterine NeoplasmsConceptsUterine 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 mutationsUterine leiomyosarcomas harboring MAP2K4 gene amplification are sensitive in vivo to PLX8725, a novel MAP2K4 inhibitor
McNamara B, Harold J, Manavella D, Bellone S, Mutlu L, Hartwich T, Zipponi M, Yang-Hartwich Y, Demirkiran C, Verzosa M, Yang K, Choi J, Dong W, Buza N, Hui P, Altwerger G, Huang G, Andikyan V, Clark M, Ratner E, Azodi M, Schwartz P, Burton E, Inagaki H, Albers A, Zhang C, Bollag G, Schlessinger J, Santin A. Uterine leiomyosarcomas harboring MAP2K4 gene amplification are sensitive in vivo to PLX8725, a novel MAP2K4 inhibitor. Gynecologic Oncology 2023, 172: 65-71. PMID: 36958197, PMCID: PMC10192120, DOI: 10.1016/j.ygyno.2023.03.009.Peer-Reviewed Original ResearchConceptsUterine leiomyosarcomaPDX modelsGain of functionMedian overall survivalPhase I trialOral gavage dailyVivo activityTumor growth inhibitionTumor volume differencesTumor cell proliferationOverall survivalTolerable toxicityI trialOral treatmentTreatment cohortsGavage dailyAggressive tumorsSCID miceULMS patientsPK studiesTumor samplesWestern blotCell proliferationControl vehicleLeiomyosarcoma
2022
Ovarian and uterine carcinosarcomas are sensitive in vitro and in vivo to elimusertib, a novel ataxia-telangiectasia and Rad3-related (ATR) kinase inhibitor
Manavella D, McNamara B, Harold J, Bellone S, Hartwich T, Yang-Hartwich Y, Mutlu L, Zipponi M, Demirkiran C, Verzosa M, Altwerger G, Ratner E, Huang G, Clark M, Andikyan V, Azodi M, Schwartz P, Dottino P, Choi J, Alexandrov L, Buza N, Hui P, Santin A. Ovarian and uterine carcinosarcomas are sensitive in vitro and in vivo to elimusertib, a novel ataxia-telangiectasia and Rad3-related (ATR) kinase inhibitor. Gynecologic Oncology 2022, 169: 98-105. PMID: 36525930, PMCID: PMC9925406, DOI: 10.1016/j.ygyno.2022.12.003.Peer-Reviewed Original ResearchConceptsHomologous recombination deficiencyCS cell linesCell linesWestern blotKinase inhibitorsOverall animal survivalProtein expressionDose-dependent increaseDose-dependent inhibitionCarcinosarcoma cell lineTumor growth inhibitionCaspase-3 expressionEndometrioid histologyAggressive malignancyUterine carcinosarcomaCS patientsPreclinical activityClinical trialsEpithelial componentAnimal survivalXenograftsApoptosis markersRecombination deficiencyP-ATRP-Chk1Elimusertib (BAY1895344), a novel ATR inhibitor, demonstrates in vivo activity in ATRX mutated models of uterine leiomyosarcoma
Harold J, Bellone S, Manavella D, Mutlu L, McNamara B, Hartwich T, Zipponi M, Yang-Hartwich Y, Demirkiran C, Verzosa M, Choi J, Dong W, Buza N, Hui P, Altwerger G, Huang G, Andikyan V, Clark M, Ratner E, Azodi M, Schwartz P, Santin A. Elimusertib (BAY1895344), a novel ATR inhibitor, demonstrates in vivo activity in ATRX mutated models of uterine leiomyosarcoma. Gynecologic Oncology 2022, 168: 157-165. PMID: 36442427, PMCID: PMC9797429, DOI: 10.1016/j.ygyno.2022.11.014.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAtaxia Telangiectasia Mutated ProteinsFemaleHumansLeiomyosarcomaMiceMice, SCIDMutationUterine NeoplasmsX-linked Nuclear ProteinConceptsPatient-derived xenograftsUterine leiomyosarcomaVivo activityVehicle control treatmentMedian overall survivalTumor volume differencesOral scheduleWestern blot analysisOverall survivalOral gavageAggressive malignancyPDX modelsClinical trialsSCID miceTumor measurementsULMS patientsSignificant growth inhibitionNovel ATR inhibitorTumor samplesSignificant toxicityWestern blotKinase inhibitorsATRX mutationsGene mutationsControl vehicle
2009
Serum amyloid A (SAA): a novel biomarker for uterine serous papillary cancer
Cocco E, Bellone S, El-Sahwi K, Cargnelutti M, Casagrande F, Buza N, Tavassoli FA, Siegel ER, Visintin I, Ratner E, Silasi DA, Azodi M, Schwartz PE, Rutherford TJ, Pecorelli S, Santin AD. Serum amyloid A (SAA): a novel biomarker for uterine serous papillary cancer. British Journal Of Cancer 2009, 101: 335-341. PMID: 19536090, PMCID: PMC2720219, DOI: 10.1038/sj.bjc.6605129.Peer-Reviewed Original ResearchConceptsUterine serous papillary carcinomaSerum amyloid AUSPC patientsBenign diseaseSAA concentrationsNovel biomarkersPrimary USPC cell linesUterine serous papillary cancerSerum SAALiver-secreted proteinsNormal healthy femalesUSPC cell linesEarly disease recurrenceSerous papillary carcinomaNormal endometrial tissuesExpression levelsProtein expression levelsEndometrial cancerAggressive variantHealthy womenEndometrial tissuePapillary cancerSerum biomarkersAmyloid AHealthy group
2005
Gene expression fingerprint of uterine serous papillary carcinoma: identification of novel molecular markers for uterine serous cancer diagnosis and therapy
Santin AD, Zhan F, Cane' S, Bellone S, Palmieri M, Thomas M, Burnett A, Roman JJ, Cannon MJ, Shaughnessy J, Pecorelli S. Gene expression fingerprint of uterine serous papillary carcinoma: identification of novel molecular markers for uterine serous cancer diagnosis and therapy. British Journal Of Cancer 2005, 92: 1561-1573. PMID: 15785748, PMCID: PMC2362016, DOI: 10.1038/sj.bjc.6602480.Peer-Reviewed Original ResearchConceptsUterine serous papillary cancerNormal endometrial cellsEndometrial cancerAggressive variantClaudin-4Normal endometrial epithelial cellsUterine serous papillary carcinomaAdhesion moleculesNovel therapeutic markerCommon gynecologic tumorsSerous papillary carcinomaParaffin-embedded specimensEndometrial epithelial cellsL1 cell adhesion moleculeType-specific therapiesRas homolog gene familyQuantitative RT-PCRScalar dosesGynecologic tumorsPapillary cancerEndometrial cellsInterleukin-6Cell adhesion moleculeNovel molecular markersPapillary carcinoma
2004
Discrimination between uterine serous papillary carcinomas and ovarian serous papillary tumours by gene expression profiling
Santin AD, Zhan F, Bellone S, Palmieri M, Cane S, Gokden M, Roman JJ, O'Brien TJ, Tian E, Cannon MJ, Shaughnessy J, Pecorelli S. Discrimination between uterine serous papillary carcinomas and ovarian serous papillary tumours by gene expression profiling. British Journal Of Cancer 2004, 90: 1814-1824. PMID: 15208622, PMCID: PMC2409747, DOI: 10.1038/sj.bjc.6601791.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedCarcinoma, PapillaryCells, CulturedCystadenocarcinoma, SerousDiagnosis, DifferentialFemaleFlow CytometryGene Expression ProfilingGene Expression Regulation, NeoplasticHumansImmunohistochemistryMiddle AgedOligonucleotide Array Sequence AnalysisOvarian NeoplasmsReceptor, ErbB-2Reverse Transcriptase Polymerase Chain ReactionUterine NeoplasmsConceptsUterine serous papillary carcinomaGene expressionOverexpressed genesSerous papillary carcinomaGene expression fingerprintGene expression profilingHuman genesC-erbB2 geneExpression fingerprintsMolecular basisExpression profilingPapillary carcinomaOligonucleotide microarraysExpression productsQuantitative RT-PCRGenesClinical tissue samplesProbe setsTwo-fold differenceMore effective treatment modalitiesEffective treatment modalitySerous papillary tumorsPlasminogen activator inhibitorDifferent biological behaviorDevelopment of novel