2023
Trastuzumab deruxtecan (DS-8201a), a HER2-targeting antibody–drug conjugate with topoisomerase I inhibitor payload, shows antitumor activity in uterine and ovarian carcinosarcoma with HER2/neu expression
Mauricio D, Bellone S, Mutlu L, McNamara B, Manavella D, Demirkiran C, Verzosa M, Buza N, Hui P, Hartwich T, Harold J, Yang-Hartwich Y, Zipponi M, Altwerger G, Ratner E, Huang G, Clark M, Andikyan V, Azodi M, Schwartz P, Santin A. Trastuzumab deruxtecan (DS-8201a), a HER2-targeting antibody–drug conjugate with topoisomerase I inhibitor payload, shows antitumor activity in uterine and ovarian carcinosarcoma with HER2/neu expression. Gynecologic Oncology 2023, 170: 38-45. PMID: 36610380, PMCID: PMC10445234, DOI: 10.1016/j.ygyno.2022.12.018.Peer-Reviewed Original ResearchConceptsHER2/neu expressionDS-8201aAntibody-drug conjugatesNeu expressionCS cell linesTrastuzumab deruxtecanOvarian carcinosarcomaTopoisomerase I inhibitor payloadCell linesAggressive gynecologic malignancyLimited therapeutic optionsEffective antibody-drug conjugatesCarcinosarcoma cell lineGynecologic malignanciesTherapeutic optionsIsotype controlSarcomatous elementsXenograft modelBystander killingFlow cytometryTumor cellsCarcinosarcomaAntitumor activityVivo studiesVivo activity
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-Chk1
2016
RNA-seq Identification of RACGAP1 as a Metastatic Driver in Uterine Carcinosarcoma
Mi S, Lin M, Brouwer-Visser J, Heim J, Smotkin D, Hebert T, Gunter MJ, Goldberg GL, Zheng D, Huang GS. RNA-seq Identification of RACGAP1 as a Metastatic Driver in Uterine Carcinosarcoma. Clinical Cancer Research 2016, 22: 4676-4686. PMID: 27121792, DOI: 10.1158/1078-0432.ccr-15-2116.Peer-Reviewed Original ResearchMeSH KeywordsAgedAged, 80 and overCarcinosarcomaCase-Control StudiesCell MovementFemaleGene ExpressionGene Expression ProfilingGTPase-Activating ProteinsHigh-Throughput Nucleotide SequencingHumansInhibitor of Apoptosis ProteinsMiddle AgedNeoplasm MetastasisNeoplasm StagingSTAT3 Transcription FactorSurvivinTranscriptomeUterine NeoplasmsConceptsUterine carcinosarcomaTherapeutic targetCell line-derived xenograft modelSurvivin expressionRare aggressive malignancyPrimary surgical resectionHigh relapse rateNormal endometrial tissuesNovel therapeutic targetCarcinosarcoma cell lineEndometrial adenocarcinoma cellsFunctional assaysCell linesExtrauterine spreadPostmenopausal womenCancer Genome AtlasMedian survivalSurgical resectionExtrauterine metastasesRelapse rateBenign indicationsEndometrial tissueAggressive malignancyPoor responseTCGA cohort