2024
Sacituzumab govitecan in heavily pretreated, platinum-resistant high grade serous ovarian cancer
Greenman M, Bellone S, Demirkiran C, Hartwich T, Santin A. Sacituzumab govitecan in heavily pretreated, platinum-resistant high grade serous ovarian cancer. Gynecologic Oncology Reports 2024, 54: 101459. PMID: 39108617, PMCID: PMC11300917, DOI: 10.1016/j.gore.2024.101459.Peer-Reviewed Original ResearchHigh grade serous ovarian cancerAntibody-drug conjugatesSerous ovarian cancerSacituzumab govitecanOvarian cancerTreatment optionsPlatinum-resistant ovarian cancer patientsDose-limiting toxicityOvarian cancer patientsNovel treatment optionsPartial responseRecurrent diseaseDose reductionCancer patientsClinical trialsBackground treatmentTargeted treatmentChemotherapyTreatmentCancerDoseDiseaseOptionsTrop2Patients
2023
Trastuzumab deruxtecan in recurrent uterine serous carcinoma resistant to trastuzmab based-chemotherapy
McNamara B, Bellone S, Demirkiran C, Hartwich T, Santin A. Trastuzumab deruxtecan in recurrent uterine serous carcinoma resistant to trastuzmab based-chemotherapy. Gynecologic Oncology Reports 2023, 48: 101219. PMID: 37325293, PMCID: PMC10265462, DOI: 10.1016/j.gore.2023.101219.Peer-Reviewed Original ResearchUterine serous carcinomaHER2/neuSerous carcinomaT-DXdTreatment optionsRecurrent uterine serous carcinomaDose-limiting side effectEffective treatment optionNew treatment optionsBone painRecurrent diseaseDurable responsesTrastuzumab deruxtecanCA 125Disease burdenSide effectsCarcinomaAntibody drugsTreatmentSignificant reductionDiseaseNeuExperimental treatmentsMetastaticPainPembrolizumab and lenvatinib in recurrent ovarian clear cell carcinoma resistant to chemotherapy
McNamara B, Bellone S, Demirkiran C, Hartwich T, Santin A. Pembrolizumab and lenvatinib in recurrent ovarian clear cell carcinoma resistant to chemotherapy. Gynecologic Oncology Reports 2023, 48: 101218. PMID: 37325296, PMCID: PMC10265468, DOI: 10.1016/j.gore.2023.101218.Peer-Reviewed Original ResearchOvarian clear cell carcinomaClear cell carcinomaCombination of pembrolizumabCell carcinomaTreatment optionsRecurrent ovarian clear cell carcinomaWeeks of therapyCT scan findingsMild side effectsEffective treatment optionOral multikinase inhibitorNew treatment optionsDurable responsesMetastatic diseaseScan findingsPD-1Disease burdenTarget lesionsMultikinase inhibitorDrug combinationsSide effectsPembrolizumabLenvatinibMonoclonal antibodiesCarcinoma
2022
Immune checkpoint inhibitors for recurrent endometrial cancer
Mutlu L, Harold J, Tymon-Rosario J, Santin AD. Immune checkpoint inhibitors for recurrent endometrial cancer. Expert Review Of Anticancer Therapy 2022, 22: 249-258. PMID: 35176955, DOI: 10.1080/14737140.2022.2044311.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsRecurrent endometrial cancerCheckpoint inhibitorsEndometrial cancerEC patientsAdvanced/recurrent endometrial cancerPD-1/PD-L1 inhibitorsRecurrent EC patientsUse of chemotherapyCommon gynecologic malignancyMajor clinical trialsPD-L1 inhibitorsBiomarkers of responseViable treatment optionHuman cancer treatmentTumor microenvironment immunosuppressionRecurrent diseaseGynecologic malignanciesPD-1Clinical efficacyPatient populationTreatment optionsTumor immunogenicityRecent trialsClinical trials
2021
DHES0815A, a novel antibody-drug conjugate targeting HER2/neu, is highly active against uterine serous carcinomas in vitro and in vivo
Tymon-Rosario J, Bonazzoli E, Bellone S, Manzano A, Pelligra S, Guglielmi A, Gnutti B, Nagarkatti N, Zeybek B, Manara P, Zammataro L, Harold J, Mauricio D, Buza N, Hui P, Altwerger G, Menderes G, Ratner E, Clark M, Andikyan V, Huang GS, Silasi DA, Azodi M, Schwartz PE, Santin AD. DHES0815A, a novel antibody-drug conjugate targeting HER2/neu, is highly active against uterine serous carcinomas in vitro and in vivo. Gynecologic Oncology 2021, 163: 334-341. PMID: 34452746, PMCID: PMC8722447, DOI: 10.1016/j.ygyno.2021.08.014.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, Monoclonal, HumanizedBenzodiazepinesBystander EffectCell Line, TumorCystadenocarcinoma, SerousDrug Resistance, NeoplasmFemaleHumansImmunoconjugatesMiddle AgedPrimary Cell CultureReceptor, ErbB-2TrastuzumabUterine NeoplasmsXenograft Model Antitumor AssaysConceptsHER2/neuPrimary USC cell linesUSC cell linesUterine serous carcinomaSerous carcinomaHER2/Cell linesBystander killingHER2/neu protein expressionHER2/neu overexpressionProtein expressionNovel treatment optionsAggressive histologic variantNeu protein expressionHER2 protein expressionC-erbB2 gene amplificationSignificant bystander killingUSC xenograftsEndometrial cancerNegative tumorsPoor prognosisPositive tumorsTreatment optionsPreclinical activityHistologic variants
2020
Targeting human epidermal growth factor receptor 2 (HER2) in gynecologic malignancies.
Erickson BK, Zeybek B, Santin AD, Fader AN. Targeting human epidermal growth factor receptor 2 (HER2) in gynecologic malignancies. Current Opinion In Obstetrics & Gynecology 2020, 32: 57-64. PMID: 31833974, PMCID: PMC7307693, DOI: 10.1097/gco.0000000000000599.Peer-Reviewed Original ResearchConceptsHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Growth factor receptor 2Uterine serous carcinomaGynecologic malignanciesFactor receptor 2Serous carcinomaReceptor 2Recurrent uterine serous carcinomaAnti-HER2 antibody trastuzumabHER2-positive diseaseAnti-HER2 therapyAnti-HER2 treatmentHER2-positive breastTrial of womenEndometrial cancer subtypesMore treatment optionsEffective therapeutic targetTreatment optionsUterine carcinosarcomaTrastuzumab efficacyHER2 amplificationTargeted therapyGastric cancerSignificant efficacy
2018
Binimetinib (MEK162) in recurrent low-grade serous ovarian cancer resistant to chemotherapy and hormonal treatment
Han C, Bellone S, Zammataro L, Schwartz PE, Santin AD. Binimetinib (MEK162) in recurrent low-grade serous ovarian cancer resistant to chemotherapy and hormonal treatment. Gynecologic Oncology Reports 2018, 25: 41-44. PMID: 29946554, PMCID: PMC6014583, DOI: 10.1016/j.gore.2018.05.011.Peer-Reviewed Original ResearchLow-grade serous ovarian carcinomaTreatment optionsHormonal treatmentRecurrent low-grade serous ovarian cancerRecurrent low-grade serous ovarian carcinomaLow-grade serous ovarian cancerDramatic clinical responseDrug-related toxicityEffective treatment optionNew treatment optionsSerial CT scansSerous ovarian cancerSerous ovarian carcinomaMitogen-activated protein kinase inhibitorOral steroidsRECIST 1.1Clinical responseMultiple chemotherapyOvarian carcinomaTarget lesionsOvarian cancerCT scanResponse durationBinimetinibKRAS G12Sacituzumab Govitecan (IMMU-132) in treatment-resistant uterine serous carcinoma: A case report
Han C, Bellone S, Schwartz PE, Govindan SV, Sharkey RM, Goldenberg DM, Santin AD. Sacituzumab Govitecan (IMMU-132) in treatment-resistant uterine serous carcinoma: A case report. Gynecologic Oncology Reports 2018, 25: 37-40. PMID: 29977989, PMCID: PMC6030029, DOI: 10.1016/j.gore.2018.05.009.Peer-Reviewed Original ResearchUterine serous carcinomaSacituzumab govitecanAntibody-drug conjugatesSerous carcinomaTreatment optionsNovel antibody-drug conjugateTreatment-resistant diseaseImpressive clinical responsesSignificant adverse eventsEffective treatment optionNew treatment optionsSerial CT scansUSC patientsAdverse eventsClinical responseMultiple chemotherapyAggressive variantCase reportUterine cancerClinical trialsCT scanDramatic responseSurface antigenTrop-2Chemotherapy
2016
Regression of metastatic, radiation/chemotherapy-resistant uterine serous carcinoma overexpressing HER2/neu with trastuzumab emtansine (TDM-1)
Santin AD, Bellone S, Buza N, Schwartz PE. Regression of metastatic, radiation/chemotherapy-resistant uterine serous carcinoma overexpressing HER2/neu with trastuzumab emtansine (TDM-1). Gynecologic Oncology Reports 2016, 19: 10-12. PMID: 28018954, PMCID: PMC5175991, DOI: 10.1016/j.gore.2016.12.003.Peer-Reviewed Original ResearchTDM-1Remarkable clinical responsesAlternative therapeutic optionUterine serous carcinomaNovel treatment optionsAbdominal wall musclesUSC patientsClinical responseTumor depositsSerous carcinomaTherapeutic optionsTreatment optionsTrastuzumab emtansineComplete resolutionCAT scanSystemic controlWall musclesPatientsCarcinomaHER2NeuChemotherapyEmtansineSurgeryOptionsRegression of Chemotherapy-Resistant Polymerase ϵ (POLE) Ultra-Mutated and MSH6 Hyper-Mutated Endometrial Tumors with Nivolumab
Santin AD, Bellone S, Buza N, Choi J, Schwartz PE, Schlessinger J, Lifton RP. Regression of Chemotherapy-Resistant Polymerase ϵ (POLE) Ultra-Mutated and MSH6 Hyper-Mutated Endometrial Tumors with Nivolumab. Clinical Cancer Research 2016, 22: 5682-5687. PMID: 27486176, PMCID: PMC5135588, DOI: 10.1158/1078-0432.ccr-16-1031.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitor nivolumabCheckpoint inhibitor nivolumabClinical responseInhibitor nivolumabAnti-PD-1 inhibitorsHyper-mutated tumorsPatient's clinical responseRemarkable clinical responsesAlternative therapeutic optionNovel treatment optionsRecurrent/metastaticHigh side effectsRecurrent diseaseEndometrial carcinomaTherapeutic optionsTreatment optionsModern chemotherapyGrade 3Side effectsPatientsHuman tumorsTumorsGene mutationsNivolumabChemotherapyThe Role of the Immune System in Ovarian Cancer and Implications on Therapy
Menderes G, Schwab CL, Black J, Santin AD. The Role of the Immune System in Ovarian Cancer and Implications on Therapy. Expert Review Of Clinical Immunology 2016, 12: 681-695. PMID: 26821930, DOI: 10.1586/1744666x.2016.1147957.Peer-Reviewed Original ResearchConceptsOvarian cancerImmune systemGoal of immunotherapyConventional cytotoxic chemotherapyCause of deathAdvanced surgical techniquesDifferent immunotherapiesTremendous toxicityCytotoxic chemotherapyGynecologic malignanciesDisease recurrenceMicroscopic diseaseTreatment optionsImmune modulationSurgical techniqueCurrent evidenceDisease pathogenesisCurrent ongoing studiesCancerImmunotherapyRecurrenceOngoing studiesChemotherapyMalignancyPathogenesis
2015
Neratinib shows efficacy in the treatment of HER2 amplified carcinosarcoma in vitro and in vivo
Schwab CL, English DP, Black J, Bellone S, Lopez S, Cocco E, Bonazzoli E, Bussi B, Predolini F, Ferrari F, Ratner E, Silasi DA, Azodi M, Rutherford T, Schwartz PE, Santin AD. Neratinib shows efficacy in the treatment of HER2 amplified carcinosarcoma in vitro and in vivo. Gynecologic Oncology 2015, 139: 112-117. PMID: 26260909, PMCID: PMC4587290, DOI: 10.1016/j.ygyno.2015.08.002.Peer-Reviewed Original ResearchConceptsHER2/neuTreatment of HER2Efficacy of neratinibCarcinosarcoma cell lineTumor growthCell linesEffective treatment optionDeadliest gynecologic malignancyG0/G1 phaseCell cycle distributionCell signaling changesActivation of S6Neratinib treatmentGynecologic malignanciesOverall survivalTreatment optionsClinical trialsXenograft growthNew therapiesHER2NeratinibFlow cytometryNeuCycle distributionSignaling changes
2014
T-DM1, a novel antibody-drug conjugate, is highly effective against uterine and ovarian carcinosarcomas overexpressing HER2
Nicoletti R, Lopez S, Bellone S, Cocco E, Schwab CL, Black JD, Centritto F, Zhu L, Bonazzoli E, Buza N, Hui P, Mezzanzanica D, Canevari S, Schwartz PE, Rutherford TJ, Santin AD. T-DM1, a novel antibody-drug conjugate, is highly effective against uterine and ovarian carcinosarcomas overexpressing HER2. Clinical & Experimental Metastasis 2014, 32: 29-38. PMID: 25398397, PMCID: PMC4310789, DOI: 10.1007/s10585-014-9688-8.Peer-Reviewed Original ResearchMeSH KeywordsAdo-Trastuzumab EmtansineAnimalsAntibodies, Monoclonal, HumanizedAntibody-Dependent Cell CytotoxicityAntineoplastic AgentsCarcinosarcomaCell Line, TumorCell ProliferationFemaleImmunoconjugatesM Phase Cell Cycle CheckpointsMaytansineMiceMice, SCIDOvarian NeoplasmsReceptor, ErbB-2TrastuzumabUterine NeoplasmsXenograft Model Antitumor AssaysConceptsCS cell linesT-DM1Cell linesFlow cytometryNovel antibody-drug conjugateAggressive clinical behaviorNovel treatment optionsG2/M phase cell cycle arrestHER2 protein overexpressionM phase cell cycle arrestPhase cell cycle arrestAntibody-drug conjugatesDisease refractoryPrimary HER2Vehicle miceOvarian carcinosarcomaPoor prognosisUterine carcinosarcomaCS patientsTreatment optionsClinical behaviorLonger survivalCell cycle arrestHER2 amplificationCarcinosarcomaNeratinib shows efficacy in the treatment of HER2/neu amplified uterine serous carcinoma in vitro and in vivo
Schwab CL, English DP, Roque DM, Bellone S, Lopez S, Cocco E, Nicoletti R, Rutherford TJ, Schwartz PE, Santin AD. Neratinib shows efficacy in the treatment of HER2/neu amplified uterine serous carcinoma in vitro and in vivo. Gynecologic Oncology 2014, 135: 142-148. PMID: 25124161, DOI: 10.1016/j.ygyno.2014.08.006.Peer-Reviewed Original ResearchConceptsHER2/neu amplificationUterine serous carcinomaHER2/neuUSC cell linesNeu amplificationNon-amplified cell linesSerous carcinomaCell linesTyrosine kinase inhibitor neratinibEffects of neratinibPrimary USC cell linesEndometrial cancer patientsPotential treatment optionEfficacy of neratinibG0/G1 phaseCell cycle distributionActivation of S6Overall survivalEndometrial cancerAggressive variantTreatment optionsCancer patientsClinical trialsPrimary cell linesHER2 inhibitors
2011
Uterine and ovarian carcinosarcomas overexpressing Trop-2 are sensitive to hRS7, a humanized anti-Trop-2 antibody
Raji R, Guzzo F, Carrara L, Varughese J, Cocco E, Bellone S, Betti M, Todeschini P, Gasparrini S, Ratner E, Silasi DA, Azodi M, Schwartz P, Rutherford TJ, Buza N, Pecorelli S, Santin AD. Uterine and ovarian carcinosarcomas overexpressing Trop-2 are sensitive to hRS7, a humanized anti-Trop-2 antibody. Journal Of Experimental & Clinical Cancer Research 2011, 30: 106. PMID: 22075385, PMCID: PMC3224774, DOI: 10.1186/1756-9966-30-106.Peer-Reviewed Original ResearchConceptsAntibody-dependent cellular cytotoxicityAnti-Trop-2 antibodyTrop-2Cell linesEffective treatment optionChromium release assaysComplement-dependent cytotoxicityCarcinosarcoma cell lineCell surface markersOvarian carcinosarcomaTreatment optionsControl antibodyHRS7Cellular cytotoxicityHigher positivityTherapeutic strategiesHuman uterineTumor tissueFlow cytometryImmunohistochemistryRT-PCRSurface expressionAntibodiesHuman IgGCarcinosarcomaerbB2 Overexpression in Uterine Serous Cancer: A Molecular Target for Trastuzumab Therapy
ElSahwi KS, Santin AD. erbB2 Overexpression in Uterine Serous Cancer: A Molecular Target for Trastuzumab Therapy. Obstetrics And Gynecology International 2011, 2011: 128295. PMID: 21876697, PMCID: PMC3159302, DOI: 10.1155/2011/128295.Peer-Reviewed Original ResearchUterine serous adenocarcinomaERBB2 overexpressionEndometrial cancerCommon female genital tract malignancyFemale genital tract malignanciesType I endometrial cancerGenital tract malignanciesUterine serous cancerViable treatment optionSerous cancerStandard chemotherapyWorse survivalLymph nodesTrastuzumab therapyBetter prognosisDistant metastasisSerous adenocarcinomaTreatment optionsCase reportRecurrent casesBreast cancerHumanized mAbTrastuzumab activityType II variantCancer relapseCervical carcinomas overexpress human trophoblast cell-surface marker (Trop-2) and are highly sensitive to immunotherapy with hRS7, a humanized monoclonal anti-Trop-2 antibody
Varughese J, Cocco E, Bellone S, Ratner E, Silasi DA, Azodi M, Schwartz PE, Rutherford TJ, Buza N, Pecorelli S, Santin AD. Cervical carcinomas overexpress human trophoblast cell-surface marker (Trop-2) and are highly sensitive to immunotherapy with hRS7, a humanized monoclonal anti-Trop-2 antibody. American Journal Of Obstetrics And Gynecology 2011, 205: 567.e1-567.e7. PMID: 21889762, PMCID: PMC3224189, DOI: 10.1016/j.ajog.2011.06.093.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdultAntibodies, MonoclonalAntigens, NeoplasmBiomarkers, TumorCarcinoma, Squamous CellCell Adhesion MoleculesCell Line, TumorComplement System ProteinsDrug Resistance, NeoplasmDrug SynergismFemaleFlow CytometryGene Expression Regulation, NeoplasticHumansImmunoglobulin GInterleukin-2Killer Cells, NaturalReal-Time Polymerase Chain ReactionUterine Cervical NeoplasmsConceptsAntibody-dependent cell-mediated cytotoxicityAnti-Trop-2 antibodyTrop-2 expressionReal-time polymerase chain reactionCell surface markersCervical cancerPolymerase chain reactionHighest messenger RNA expressionCell-dependent cytotoxicityCell-mediated cytotoxicityNovel treatment optionsChromium release assaysConventional treatment modalitiesChain reactionComplement-dependent cytotoxicityEffects of interleukinMessenger RNA expressionLevel of cytotoxicityCancer refractoryCervical carcinomaTreatment optionsTreatment modalitiesIL-2Normal cervixRelease assays
2010
High-grade, chemotherapy-resistant ovarian carcinomas overexpress epithelial cell adhesion molecule (EpCAM) and are highly sensitive to immunotherapy with MT201, a fully human monoclonal anti-EpCAM antibody
Richter CE, Cocco E, Bellone S, Silasi DA, Rüttinger D, Azodi M, Schwartz PE, Rutherford TJ, Pecorelli S, Santin AD. High-grade, chemotherapy-resistant ovarian carcinomas overexpress epithelial cell adhesion molecule (EpCAM) and are highly sensitive to immunotherapy with MT201, a fully human monoclonal anti-EpCAM antibody. American Journal Of Obstetrics And Gynecology 2010, 203: 582.e1-582.e7. PMID: 20870202, PMCID: PMC2993821, DOI: 10.1016/j.ajog.2010.07.041.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntigens, NeoplasmAntineoplastic AgentsBiomarkers, TumorCell Adhesion MoleculesCell Line, TumorDrug Resistance, NeoplasmFemaleFlow CytometryHumansImmunotherapyNeoplasm StagingOvarian NeoplasmsReverse Transcriptase Polymerase Chain ReactionRNA, MessengerSensitivity and SpecificityConceptsAntibody-dependent cell-mediated cytotoxicityComplement-dependent cytotoxicityReal-time polymerase chain reactionEpithelial cell adhesion moleculePolymerase chain reactionOvarian carcinomaInterleukin-2Cell adhesion moleculeFlow cytometryHighest messenger RNA expressionCell linesAdhesion moleculesCell-mediated cytotoxicityOvarian cancer cell linesEffective treatment optionChromium release assaysChain reactionMessenger RNA expressionCancer cell linesOvarian diseaseTreatment optionsOvarian cancerEpCAM expressionAnti-EpCAM antibodyRNA expressionHER-2/NEU overexpression in vulvar Paget disease: the Yale experience
Richter CE, Hui P, Buza N, Silasi DA, Azodi M, Santin AD, Schwartz PE, Rutherford TJ. HER-2/NEU overexpression in vulvar Paget disease: the Yale experience. Journal Of Clinical Pathology 2010, 63: 544. PMID: 20418225, DOI: 10.1136/jcp.2010.077446.Peer-Reviewed Original ResearchConceptsVulvar Paget's diseasePaget's diseaseNeu overexpressionOutcome dataHER-2/neu expressionHER-2/neuEfficacy of trastuzumabExtensive reconstructive proceduresHigh recurrence rateMedical record searchInteresting treatment optionSurgical treatmentRecurrence rateTreatment optionsNeu expressionClinical trialsReconstructive proceduresTissue microarrayPatientsRecord searchTumor samplesYale experienceDiseaseNeuStaining results