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
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
2017
SYD985, a Novel Duocarmycin-Based HER2-Targeting Antibody–Drug Conjugate, Shows Antitumor Activity in Uterine and Ovarian Carcinosarcoma with HER2/Neu Expression
Menderes G, Bonazzoli E, Bellone S, Black J, Predolini F, Pettinella F, Masserdotti A, Zammataro L, Altwerger G, Buza N, Hui P, Wong S, Litkouhi B, Ratner E, Silasi DA, Azodi M, Schwartz PE, Santin AD. SYD985, a Novel Duocarmycin-Based HER2-Targeting Antibody–Drug Conjugate, Shows Antitumor Activity in Uterine and Ovarian Carcinosarcoma with HER2/Neu Expression. Clinical Cancer Research 2017, 23: 5836-5845. PMID: 28679774, PMCID: PMC5626613, DOI: 10.1158/1078-0432.ccr-16-2862.Peer-Reviewed Original ResearchMeSH KeywordsAdo-Trastuzumab EmtansineAnimalsAntibody-Dependent Cell CytotoxicityCarcinosarcomaCell Line, TumorCell ProliferationDuocarmycinsFemaleGene Expression Regulation, NeoplasticHumansImmunoconjugatesIndolesMaytansineMiceOvarian NeoplasmsPyrrolidinonesReceptor, ErbB-2TrastuzumabUterine NeoplasmsXenograft Model Antitumor AssaysConceptsAntibody-dependent cellular cytotoxicityHER2/neu expressionHER2/neu 3T-DM1Antibody-drug conjugatesCS cell linesNeu expressionEffector cellsHigh HER2/neu expressionNeu 3HER2-targeting antibody-drug conjugateCell linesBystander killingPatient-derived xenograft modelsNovel HER2-targeting antibody-drug conjugateAggressive gynecologic malignancyHigh HER2 expressionEffective antibody-drug conjugatesHER2/neuClin Cancer ResGynecologic malignanciesOvarian carcinosarcomaHER2 expressionTrastuzumab emtansineSYD985Superior in vitro and in vivo activity of trastuzumab-emtansine (T-DM1) in comparison to trastuzumab, pertuzumab and their combination in epithelial ovarian carcinoma with high HER2/neu expression
Menderes G, Bonazzoli E, Bellone S, Altwerger G, Black JD, Dugan K, Pettinella F, Masserdotti A, Riccio F, Bianchi A, Zammataro L, de Haydu C, Buza N, Hui P, Wong S, Huang GS, Litkouhi B, Ratner E, Silasi DA, Azodi M, Schwartz PE, Santin AD. Superior in vitro and in vivo activity of trastuzumab-emtansine (T-DM1) in comparison to trastuzumab, pertuzumab and their combination in epithelial ovarian carcinoma with high HER2/neu expression. Gynecologic Oncology 2017, 147: 145-152. PMID: 28705408, PMCID: PMC5605415, DOI: 10.1016/j.ygyno.2017.07.009.Peer-Reviewed Original ResearchConceptsHigh HER2/neu expressionHER2/neu expressionEpithelial ovarian cancerHER2/neuAnti-tumor activityEOC cell linesT-DM1Neu expressionChemotherapy-resistant epithelial ovarian cancerLimited anti-tumor activityAntibody-dependent cell-mediated cytotoxicity (ADCC) activityCell linesSuperior anti-tumor activityCombination of trastuzumabLethal gynecologic malignancyEpithelial ovarian carcinomaTumor growth inhibitionEOC xenograftsGynecologic malignanciesPreclinical dataOvarian carcinomaOvarian cancerClinical studiesXenograft modelSingle agentSYD985, a novel duocarmycin-based HER2-targeting antibody-drug conjugate, shows promising antitumor activity in epithelial ovarian carcinoma with HER2/neu expression.
Menderes G, Bonazzoli E, Bellone S, Black J, Altwerger G, Pettinella F, Masserdotti A, Zammataro L, Buza N, Hui P, Wong S, Litkouhi B, Ratner E, Silasi D, Azodi M, Schwartz P, Santin A. SYD985, a novel duocarmycin-based HER2-targeting antibody-drug conjugate, shows promising antitumor activity in epithelial ovarian carcinoma with HER2/neu expression. Journal Of Clinical Oncology 2017, 35: e14009-e14009. DOI: 10.1200/jco.2017.35.15_suppl.e14009.Peer-Reviewed Original ResearchHER2/neu expressionHER2/neu 3Epithelial ovarian cancerAntibody-dependent cellular cytotoxicityAntibody-drug conjugatesT-DM1Neu expressionEOC cell linesNeu 3Low HER2/neu expressionHER2/neu 2HER2-targeting antibody-drug conjugateHER2 overexpression/amplificationNovel antibody-drug conjugateNovel HER2-targeting antibody-drug conjugateCell linesChemo-resistant diseaseEpithelial ovarian carcinomaOvarian cancer xenograftsLethal gynecological cancerOverexpression/amplificationAnti-tumor activityMonoclonal antibody trastuzumabEffector cellsEOC patientsSYD985, a novel duocarmycin-based HER2-targeting antibody-drug conjugate, shows promising antitumor activity in epithelial ovarian carcinoma with HER2/Neu expression
Menderes G, Bonazzoli E, Bellone S, Black J, Altwerger G, Masserdotti A, Pettinella F, Zammataro L, Buza N, Hui P, Wong S, Litkouhi B, Ratner E, Silasi DA, Huang GS, Azodi M, Schwartz PE, Santin AD. SYD985, a novel duocarmycin-based HER2-targeting antibody-drug conjugate, shows promising antitumor activity in epithelial ovarian carcinoma with HER2/Neu expression. Gynecologic Oncology 2017, 146: 179-186. PMID: 28473206, PMCID: PMC5533304, DOI: 10.1016/j.ygyno.2017.04.023.Peer-Reviewed Original ResearchMeSH KeywordsAdo-Trastuzumab EmtansineAdultAgedAnimalsAntibodies, Monoclonal, HumanizedAntibody-Dependent Cell CytotoxicityAntineoplastic Agents, AlkylatingBystander EffectCarcinoma, Ovarian EpithelialCell Line, TumorDuocarmycinsFemaleHumansImmunotoxinsIndolesMaytansineMiceMice, SCIDMiddle AgedNeoplasms, Glandular and EpithelialOvarian NeoplasmsPyrrolidinonesRandom AllocationReceptor, ErbB-2TrastuzumabXenograft Model Antitumor AssaysConceptsHER2/neu expressionAntibody-dependent cellular cytotoxicityEpithelial ovarian cancerLow HER2/neu expressionPeripheral blood lymphocytesHER2/neu 3Antibody-drug conjugatesT-DM1Neu expressionEOC cell linesNeu 3HER2-targeting antibody-drug conjugateNovel antibody-drug conjugateNovel HER2-targeting antibody-drug conjugateEpithelial ovarian carcinomaOvarian cancer xenograftsAnti-tumor activityCell linesEOC xenograftsTrastuzumab emtansineCancer xenograftsBlood lymphocytesOvarian cancerOvarian carcinomaSYD985
2016
SYD985, a Novel Duocarmycin-Based HER2-Targeting Antibody–Drug Conjugate, Shows Antitumor Activity in Uterine Serous Carcinoma with HER2/Neu Expression
Black J, Menderes G, Bellone S, Schwab CL, Bonazzoli E, Ferrari F, Predolini F, De Haydu C, Cocco E, Buza N, Hui P, Wong S, Lopez S, Ratner E, Silasi DA, Azodi M, Litkouhi B, Schwartz PE, Goedings P, Beusker PH, van der Lee MM, Timmers CM, Dokter WH, Santin AD. SYD985, a Novel Duocarmycin-Based HER2-Targeting Antibody–Drug Conjugate, Shows Antitumor Activity in Uterine Serous Carcinoma with HER2/Neu Expression. Molecular Cancer Therapeutics 2016, 15: 1900-1909. PMID: 27256376, DOI: 10.1158/1535-7163.mct-16-0163.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAnimalsAntibody-Dependent Cell CytotoxicityAntineoplastic AgentsBystander EffectCathepsin BCell Line, TumorCell SurvivalClass I Phosphatidylinositol 3-KinasesCystadenocarcinoma, SerousDisease Models, AnimalDuocarmycinsFemaleGene ExpressionHumansImmunoconjugatesIndolesMiceMiddle AgedMutationPhosphatidylinositol 3-KinasesPyrrolidinonesReceptor, ErbB-2Survival AnalysisUterine NeoplasmsXenograft Model Antitumor AssaysConceptsUterine serous carcinomaAntibody-dependent cellular cytotoxicityHER2/neu expressionAntibody-drug conjugatesT-DM1Neu expressionHER2-targeting antibody-drug conjugateNovel antibody-drug conjugateNovel HER2-targeting antibody-drug conjugatePrimary USC cell linesHigh HER2 expressionHER2/neu oncogeneHER2/neuMouse xenograft modelUSC cell linesFlow cytometry assayEndometrial cancerSerous carcinomaHER2 expressionTrastuzumab emtansineClinical studiesCellular cytotoxicitySYD985Aggressive formExpress HER2
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
2009
In vitro activity of pertuzumab in combination with trastuzumab in uterine serous papillary adenocarcinoma
El-Sahwi K, Bellone S, Cocco E, Cargnelutti M, Casagrande F, Bellone M, Abu-Khalaf M, Buza N, Tavassoli FA, Hui P, Silasi DA, Azodi M, Schwartz PE, Rutherford TJ, Pecorelli S, Santin AD. In vitro activity of pertuzumab in combination with trastuzumab in uterine serous papillary adenocarcinoma. British Journal Of Cancer 2009, 102: 134-143. PMID: 19920829, PMCID: PMC2813756, DOI: 10.1038/sj.bjc.6605448.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinoma, PapillaryAgedAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntibody-Dependent Cell CytotoxicityCell Line, TumorComplement System ProteinsCytotoxicity, ImmunologicDimerizationDrug Screening Assays, AntitumorDrug SynergismFemaleHumansImmunoglobulin GIn Vitro TechniquesInterleukin-2Killer Cells, NaturalLymphocytesMiddle AgedReceptor, ErbB-2Signal TransductionTrastuzumabUterine NeoplasmsConceptsAntibody-dependent cell-mediated cytotoxicityUSPC cell linesHER2/neu expressionComplement-dependent cytotoxicityStrong antibody-dependent cell-mediated cytotoxicitySerous papillary adenocarcinomaNeu expressionHER2/neuPapillary adenocarcinomaHigh HER2/neu expressionLow HER2/neu expressionCell linesH chromium release assaysPrimary USPC cell linesAdvanced/recurrentCombination of pertuzumabCell-mediated cytotoxicityHumanised monoclonal antibodyChromium release assaysC-erbB2 gene amplificationActivity of pertuzumabNew therapeutic agentsProliferation-based assaysType II receptorEndometrial cancer