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 chemotherapy
2020
Cervical carcinomas that overexpress human trophoblast cell-surface marker (Trop-2) are highly sensitive to the antibody-drug conjugate sacituzumab govitecan
Zeybek B, Manzano A, Bianchi A, Bonazzoli E, Bellone S, Buza N, Hui P, Lopez S, Perrone E, Manara P, Zammataro L, Altwerger G, Han C, Tymon-Rosario J, Menderes G, Ratner E, Silasi DA, Huang GS, Azodi M, Schwartz PE, Santin A. Cervical carcinomas that overexpress human trophoblast cell-surface marker (Trop-2) are highly sensitive to the antibody-drug conjugate sacituzumab govitecan. Scientific Reports 2020, 10: 973. PMID: 31969666, PMCID: PMC6976591, DOI: 10.1038/s41598-020-58009-3.Peer-Reviewed Original ResearchConceptsSquamous cell carcinomaSacituzumab govitecanTrop-2 expressionAntibody-drug conjugatesCell surface markersXenograft modelTrop-2Adenocarcinoma/adenosquamous carcinomaAnti-Trop-2 antibodyCell linesWeekly intravenous administrationSignificant tumor growth inhibitionCervical cancer patientsPrimary cervical cancerStrong diffuse stainingPrimary cervical tumorsCervical cancer cell linesEpithelial solid tumorsReal-time polymerase chain reactionTumor growth inhibitionHuman placental tissuePositive cell linesNegative cell linesVivo antitumor activityCancer cell linesSacituzumab govitecan, an antibody‐drug conjugate targeting trophoblast cell‐surface antigen 2, shows cytotoxic activity against poorly differentiated endometrial adenocarcinomas in vitro and in vivo
Perrone E, Manara P, Lopez S, Bellone S, Bonazzoli E, Manzano A, Zammataro L, Bianchi A, Zeybek B, Buza N, Tymon‐Rosario J, Altwerger G, Han C, Menderes G, Huang GS, Ratner E, Silasi D, Azodi M, Hui P, Schwartz PE, Scambia G, Santin AD. Sacituzumab govitecan, an antibody‐drug conjugate targeting trophoblast cell‐surface antigen 2, shows cytotoxic activity against poorly differentiated endometrial adenocarcinomas in vitro and in vivo. Molecular Oncology 2020, 14: 645-656. PMID: 31891442, PMCID: PMC7053235, DOI: 10.1002/1878-0261.12627.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, Monoclonal, HumanizedAntibody-Dependent Cell CytotoxicityAntigens, NeoplasmAntineoplastic AgentsCamptothecinCarcinoma, EndometrioidCell Adhesion MoleculesCell DifferentiationCell Line, TumorCell SurvivalEndometrial NeoplasmsFemaleHumansImmunoconjugatesImmunohistochemistryIrinotecanMiceMice, SCIDTissue Array AnalysisXenograft Model Antitumor AssaysConceptsAntibody-dependent cell cytotoxicityCell surface antigen 2EC cell linesSacituzumab govitecanTrop-2 expressionPrimary tumor cell linesTrop-2Xenograft modelAntigen 2Cell linesTumor cell linesCommon gynecologic malignancyFuture clinical trialsChromium release assaysParaffin-embedded tumorsTumor growth inhibitionSignificant bystander killingEC xenograftsGynecologic malignanciesEndometrial cancerEndometrial adenocarcinomaEndometrioid carcinoma tissuesPreclinical activityControl antibodyClinical trials
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