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 chemotherapyUterine 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 vehicleLeiomyosarcomaRacial disparities in diagnostic evaluation of uterine cancer among Medicaid beneficiaries
Xu X, Chen L, Nunez-Smith M, Clark M, Wright J. Racial disparities in diagnostic evaluation of uterine cancer among Medicaid beneficiaries. Journal Of The National Cancer Institute 2023, 115: 636-643. PMID: 36788453, PMCID: PMC10248843, DOI: 10.1093/jnci/djad027.Peer-Reviewed Original ResearchMeSH KeywordsBlack or African AmericanFemaleHealthcare DisparitiesHumansMedicaidUnited StatesUterine NeoplasmsWhiteConceptsAbnormal uterine bleedingWhite patientsUterine cancerFirst diagnostic procedureDiagnostic evaluationBlack patientsDiagnostic proceduresBlack-White disparitiesManagement visitsMarketScan Multi-State Medicaid DatabaseMulti-State Medicaid DatabaseUterine bleedingPatient characteristicsMedicaid databaseEarly diagnosisMedicaid beneficiariesMultivariable regressionPatientsCancerRacial disparitiesDiagnosisVisitsMore evaluationDisparitiesBleeding
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
2021
Integrated mutational landscape analysis of uterine leiomyosarcomas
Choi J, Manzano A, Dong W, Bellone S, Bonazzoli E, Zammataro L, Yao X, Deshpande A, Zaidi S, Guglielmi A, Gnutti B, Nagarkatti N, Tymon-Rosario JR, Harold J, Mauricio D, Zeybek B, Menderes G, Altwerger G, Jeong K, Zhao S, Buza N, Hui P, Ravaggi A, Bignotti E, Romani C, Todeschini P, Zanotti L, Odicino F, Pecorelli S, Ardighieri L, Bilguvar K, Quick CM, Silasi DA, Huang GS, Andikyan V, Clark M, Ratner E, Azodi M, Imielinski M, Schwartz PE, Alexandrov LB, Lifton RP, Schlessinger J, Santin AD. Integrated mutational landscape analysis of uterine leiomyosarcomas. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2025182118. PMID: 33876771, PMCID: PMC8053980, DOI: 10.1073/pnas.2025182118.Peer-Reviewed Original ResearchConceptsHomologous recombination DNA repair deficiencySequencing dataWhole-genome sequencing dataRNA sequencing dataTCGA samplesCopy number variation analysisATRX/DAXXCopy number lossNumber variation analysisDNA repair deficiencyWhole-exome sequencing dataRecurrent somatic mutationsCopy number gainsCancer Genome AtlasPatient-derived xenograftsTumor suppressorAkt geneGenetic landscapeHRD signaturesPTEN geneGenesMost fusionsC-MycMutational signaturesC-myc/
2016
Novel targeted therapies in uterine serous carcinoma, an aggressive variant of endometrial cancer.
Menderes G, Clark M, Santin AD. Novel targeted therapies in uterine serous carcinoma, an aggressive variant of endometrial cancer. Discovery Medicine 2016, 21: 293-303. PMID: 27232515.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalAntineoplastic AgentsClass I Phosphatidylinositol 3-KinasesCyclin ECystadenocarcinoma, SerousEndometrial NeoplasmsEpothilonesExomeFemaleHumansMolecular Targeted TherapyMutationNeoplasm Recurrence, LocalOncogene ProteinsPrognosisProtein Kinase InhibitorsProtein Phosphatase 2RadioimmunotherapyReceptor, ErbB-2Sequence Analysis, DNASignal TransductionTOR Serine-Threonine KinasesTubulin ModulatorsTumor Suppressor Protein p53Uterine NeoplasmsVascular Endothelial Growth Factor AConceptsUterine serous carcinomaEndometrial cancerSerous carcinomaTreatment of USCPIK3CA/AKT/mTOREndometrial cancer casesRecent whole-exome sequencing studiesHER2/neu geneNovel therapeutic targetAkt/mTORBiologic therapyAggressive variantDismal prognosisAggressive subtypeWhole-exome sequencing studiesCancer casesTherapeutic targetSubsequent deathDriver mutationsNeu geneGain of functionCarcinomaTherapyCancerSequencing studies
2015
Transvaginal Morcellation
Donat L, Clark M, Tower AM, Menderes G, Parkash V, Silasi DA, Azodi M. Transvaginal Morcellation. JSLS Journal Of The Society Of Laparoscopic & Robotic Surgeons 2015, 19: e2014.00255. PMID: 26005318, PMCID: PMC4432719, DOI: 10.4293/jsls.2014.00255.Peer-Reviewed Original ResearchConceptsTransvaginal morcellationLaparoscopic hysterectomyLeiomyomatous uterusUterine morcellationRobot-assisted laparoscopic hysterectomyLaparoscopic-assisted vaginal hysterectomyCharts of womenLarge uterine specimensMean uterine sizeMean blood lossRetrospective case seriesTotal laparoscopic hysterectomyWedge resection techniqueBaseline demographicsPostoperative outcomesSelect patientsSurgical complicationsBlood lossUterine sizeVaginal hysterectomyCase seriesOperative timeInstitution experienceMalignant entitiesMorcellation technique