2024
Unmet needs in cervical cancer – can biological therapies plug the gap?
Greenman M, Chang Y, McNamara B, Mutlu L, Santin A. Unmet needs in cervical cancer – can biological therapies plug the gap? Expert Opinion On Biological Therapy 2024, 24: 995-1003. PMID: 39311611, DOI: 10.1080/14712598.2024.2408754.Peer-Reviewed Original ResearchBiologic therapyCervical cancerIntroduction of biologic therapiesManagement of cervical cancerImmune checkpoint inhibitorsIncreased overall survivalCurrent treatment recommendationsMultiple tumor typesAntibody-drug conjugatesCheckpoint inhibitorsOverall survivalRecurrent diseaseGynecologic malignanciesTreat malignanciesTumor typesClinical outcomesAngiogenesis inhibitorsBurden of casesTreatment recommendationsTherapyImprove current standardsAntitumor activityInadequate screeningCancerMalignancyTargetable ERBB2/HER2 Mutations in Gynecologic Malignancies: Clinicopathological, Immunohistochemical, and Molecular Correlations.
Manrai P, McHenry A, Sun T, Santin A, Ratner E, Lin D, Elvin J, Hui P, Buza N. Targetable ERBB2/HER2 Mutations in Gynecologic Malignancies: Clinicopathological, Immunohistochemical, and Molecular Correlations. International Journal Of Gynecological Pathology 2024 PMID: 38914011, DOI: 10.1097/pgp.0000000000001050.Peer-Reviewed Original ResearchEndometrial carcinomaGynecologic malignanciesTyrosine kinase domainHER2-mutated non-small cell lung cancerTargeted anti-HER2 therapyNon-small cell lung cancerHigh-grade endometrioid adenocarcinomasFam-trastuzumab deruxtecanOvarian mucinous adenocarcinomaAnti-HER2 therapyAnti-HER2 drugsHER2 3+US Food and Drug AdministrationCell lung cancerEndometrial serous carcinomaSolid tumor typesStandard treatment recommendationsFood and Drug AdministrationFluorescence in situ hybridizationGynecological cancer typesEndometrial primaryMullerian originSerous carcinomaHER2 IHCEndometrioid adenocarcinoma
2023
Antibody–Drug Conjugates (ADC) in HER2/neu-Positive Gynecologic Tumors
McNamara B, Greenman M, Pebley N, Mutlu L, Santin A. Antibody–Drug Conjugates (ADC) in HER2/neu-Positive Gynecologic Tumors. Molecules 2023, 28: 7389. PMID: 37959808, PMCID: PMC10650896, DOI: 10.3390/molecules28217389.Peer-Reviewed Original ResearchConceptsHuman epidermal growth factor 2Antibody-drug conjugatesGynecologic tumorsEpidermal growth factor 2Receptor-targeting antibodiesOngoing clinical trialsRelevant preclinical studiesAnti-cancer therapyADC resistanceGynecologic malignanciesGrowth factor 2Cytotoxic therapyADC therapyClinical trialsPreclinical studiesTumor cellsTherapyTumor surface receptorsDrug conjugatesHealthy tissueFactor 2Surface receptorsTumorsTargeted deliveryDeliveryValue of Antibody Drug Conjugates for Gynecological Cancers: A Modern Appraisal Following Recent FDA Approvals
McNamara B, Chang Y, Goreshnik A, Santin A. Value of Antibody Drug Conjugates for Gynecological Cancers: A Modern Appraisal Following Recent FDA Approvals. International Journal Of Women's Health 2023, 15: 1353-1365. PMID: 37663226, PMCID: PMC10474218, DOI: 10.2147/ijwh.s400537.Peer-Reviewed Original ResearchAntibody-drug conjugatesReceptor-targeting antibodiesOngoing clinical trialsDrug conjugatesRelevant preclinical studiesRecent FDA approvalAnti-cancer therapyGynecologic malignanciesCytotoxic therapyGynecological cancerADC therapyClinical trialsPreclinical studiesFDA approvalTumor cellsTherapyHealthy tissueModern appraisalDeliveryMalignancyCancerConjugatesTrialsAntibodiesTrastuzumab 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
Advances in antibody-drug conjugates for gynecologic malignancies
Tymon-Rosario J, Gorman M, Richardson D, Washington C, Santin A. Advances in antibody-drug conjugates for gynecologic malignancies. Current Opinion In Obstetrics & Gynecology 2022, 35: 6-14. PMID: 36484278, DOI: 10.1097/gco.0000000000000838.Peer-Reviewed Original ResearchConceptsAntibody-drug conjugatesOvarian cancer patientsGynecologic malignanciesCancer patientsPlatinum-resistant ovarian cancer patientsUse of ADCsOngoing phase 3 trialsRecurrent ovarian cancer patientsNovel antibody-drug conjugateReceptor-targeting antibodiesPhase 3 trialProgression-free survivalFirst U.S. FoodOngoing clinical trialsHER2/neuPersonalized cancer careTisotumab vedotinPrimary endpointCervical cancerGynecologic cancerCancer careClinical trialsMultiple tumorsCurrent evidenceDrug AdministrationEndometrial Cancer in Reproductive Age: Fertility-Sparing Approach and Reproductive Outcomes
Mutlu L, Manavella D, Gullo G, McNamara B, Santin A, Patrizio P. Endometrial Cancer in Reproductive Age: Fertility-Sparing Approach and Reproductive Outcomes. Cancers 2022, 14: 5187. PMID: 36358604, PMCID: PMC9656291, DOI: 10.3390/cancers14215187.Peer-Reviewed Original ResearchFertility-preserving approachEndometrial cancerLow-grade endometrial cancerFertility sparing approachStandard surgical treatmentCommon gynecologic malignancyGynecologic malignanciesOncologic outcomesSurgical treatmentPatient goalsReproductive ageReproductive outcomesClose monitoringCancerYoung womenConservative approachFertility goalsReproductive technologiesPatientsWomenAgeOutcomesEarly stagesHysterectomyMalignancyImmune 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
Financial toxicity in patients with gynecologic malignancies: a cross sectional study
Zeybek B, Webster E, Pogosian N, Tymon-Rosario J, Balch A, Altwerger G, Clark M, Menderes G, Huang G, Azodi M, Ratner ES, Schwartz PE, Santin AD, Andikyan V. Financial toxicity in patients with gynecologic malignancies: a cross sectional study. Journal Of Gynecologic Oncology 2021, 32: e87. PMID: 34431257, PMCID: PMC8550931, DOI: 10.3802/jgo.2021.32.e87.Peer-Reviewed Original ResearchConceptsCross-sectional studyGynecologic malignanciesFinancial toxicityPatient demographicsSectional studyMalignancy typeGynecologic oncology patientsOvarian cancer patientsPatient/diseaseCost of careFinancial burdenHigh financial burdenTreatment regimenHigh financial toxicityOncology patientsDisease characteristicsGynecologic cancerCancer careCancer patientsRisk factorsClinical trialsCOST scoreMedian COST scorePatientsSignificant burdenNovel mesothelin antibody-drug conjugates: current evidence and future role in the treatment of ovarian cancer
Mauricio D, Harold J, Tymon-Rosario JR, Zeybek B, Santin AD. Novel mesothelin antibody-drug conjugates: current evidence and future role in the treatment of ovarian cancer. Expert Opinion On Biological Therapy 2021, 21: 1087-1096. PMID: 33356644, DOI: 10.1080/14712598.2021.1869210.Peer-Reviewed Original ResearchConceptsAntibody-drug conjugatesOvarian cancerProgressive diseaseFavorable adverse effect profilePromising novel therapeutic agentAdverse effect profilePhase II trialDeadliest gynecologic malignancyPhase III dataNovel therapeutic agentsII trialGynecologic malignanciesEffect profileClinical resultsEffective therapyAvailable agentsCurrent evidenceNovel treatmentsChemotherapeutic agentsCancerTherapeutic agentsAdverse effectsMesothelinVivo dataDisease
2020
Prescribed medical cannabis in women with gynecologic malignancies: A single-institution survey-based study
Webster EM, Yadav GS, Gysler S, McNamara B, Black J, Tymon-Rosario J, Zeybek B, Han C, Arkfeld CK, Andikyan V, Menderes G, Huang G, Azodi M, Silasi DA, Santin AD, Schwartz PE, Ratner ES, Altwerger G. Prescribed medical cannabis in women with gynecologic malignancies: A single-institution survey-based study. Gynecologic Oncology Reports 2020, 34: 100667. PMID: 33204797, PMCID: PMC7653050, DOI: 10.1016/j.gore.2020.100667.Peer-Reviewed Original ResearchTreatment-related symptomsGynecologic malignanciesMedical cannabisOpioid usePatient experienceBetter side effect profileDecrease opioid useGynecologic oncology populationPercent of patientsSide effect profileSubset of patientsBone painEligible patientsAbdominal painNeuropathic painRecurrent diseaseSymptom controlJoint painAdjunct therapyOncology populationEffect profileGynecologic oncologistsTraditional medicationsPainPatientsNovel antibody-drug conjugates: current and future roles in gynecologic oncology.
Tymon-Rosario J, Zeybek B, Santin AD. Novel antibody-drug conjugates: current and future roles in gynecologic oncology. Current Opinion In Obstetrics & Gynecology 2020, 33: 26-33. PMID: 32618744, PMCID: PMC8253558, DOI: 10.1097/gco.0000000000000642.Peer-Reviewed Original ResearchConceptsAntibody-drug conjugatesAntigen-negative cellsNovel antibody-drug conjugateAggressive gynecologic malignancyReceptor-targeting antibodiesTrop-2 overexpressionOngoing clinical trialsHER2/neuPersonalized cancer careNormal surrounding tissueAntigen-positive target cellsGynecologic malignanciesGynecologic tumorsCervical cancerSacituzumab govitecanCancer careGynecologic oncologyPreclinical dataTrastuzumab emtansineADC therapyClinical trialsMultiple tumorsCurrent standard practiceNoncleavable linkerCytotoxic moleculesPreclinical Activity of Sacituzumab Govitecan, an Antibody-Drug Conjugate Targeting Trophoblast Cell-Surface Antigen 2 (Trop-2) Linked to the Active Metabolite of Irinotecan (SN-38), in Ovarian Cancer
Perrone E, Lopez S, Zeybek B, Bellone S, Bonazzoli E, Pelligra S, Zammataro L, Manzano A, Manara P, Bianchi A, Buza N, Tymon-Rosario J, Altwerger G, Han C, Menderes G, Ratner E, Silasi DA, Azodi M, Hui P, Schwartz PE, Scambia G, Santin AD. Preclinical Activity of Sacituzumab Govitecan, an Antibody-Drug Conjugate Targeting Trophoblast Cell-Surface Antigen 2 (Trop-2) Linked to the Active Metabolite of Irinotecan (SN-38), in Ovarian Cancer. Frontiers In Oncology 2020, 10: 118. PMID: 32117765, PMCID: PMC7028697, DOI: 10.3389/fonc.2020.00118.Peer-Reviewed Original ResearchTrop-2 expressionEOC cell linesSacituzumab govitecanEpithelial ovarian cancerPrimary tumor cell linesPreclinical activityTrop-2EOC xenograftsOvarian cancerTrophoblast cell surface antigen 2Cell linesActive metaboliteTumor cell linesImpressive anti-tumor activityCell surface antigen 2Lethal gynecologic malignancyHigh ADCC activityAnti-tumor activityParaffin-embedded tumorsSignificant bystander killingGynecologic malignanciesADCC activityEOC tissuesOvarian tumorsClinical trialsTargeting 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 efficacySacituzumab 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
93 Sacituzumab govitecan in uterine and ovarian carcinosarcomas
Lopez S, Perrone E, Zeybek B, Bellone S, Manzano A, Zammataro L, Han C, Altwerger G, Angioli R, Santin A. 93 Sacituzumab govitecan in uterine and ovarian carcinosarcomas. International Journal Of Gynecological Cancer 2019, 29: a48. DOI: 10.1136/ijgc-2019-igcs.93.Peer-Reviewed Original ResearchCS cell linesAntibody-drug conjugatesSacituzumab govitecanTrop-2 expressionTrop-2Negative tumorsCell linesControl antibody drug conjugatesNovel antibody-drug conjugateAggressive gynecologic malignancyGreater antitumor effectPrimary tumor cell linesRemarkable antitumor activityAggressive carcinosarcomasGynecologic malignanciesOvarian carcinosarcomaPrimary tumorClinical trialsEpithelial tumorsSarcomatous elementsAntitumor effectsAntigen 2CarcinosarcomaActive metaboliteSN-3851 In vitro and in vivo activity of sacituzumab govitecan, in ovarian cancer
Perrone E, Lopez S, Zeibek B, Bellone S, Zammataro L, Manzano A, Bonazzoli E, Manara P, Scambia G, Santin A. 51 In vitro and in vivo activity of sacituzumab govitecan, in ovarian cancer. International Journal Of Gynecological Cancer 2019, 29: a29. DOI: 10.1136/ijgc-2019-igcs.51.Peer-Reviewed Original ResearchEpithelial ovarian cancerTrop-2 expressionSacituzumab govitecanPrimary tumor cell linesEOC cell linesTrop-2EOC xenograftsOvarian cancerCell linesTumor cell linesAggressive epithelial ovarian cancerLethal gynecologic malignancyHigh ADCC activityGreater antitumor effectParaffin-embedded tumorsGynecologic malignanciesADCC activityOvarian tumorsPreclinical activityClinical trialsEpithelial tumorsSignificant bystander effectAntitumor effectsStrong stainingActive metaboliteHuman Ovarian Cancer Tumor Formation in Severe Combined Immunodeficient (SCID) Pigs
Boettcher AN, Kiupel M, Adur MK, Cocco E, Santin AD, Bellone S, Charley SE, Blanco-Fernandez B, Risinger JI, Ross JW, Tuggle CK, Shapiro EM. Human Ovarian Cancer Tumor Formation in Severe Combined Immunodeficient (SCID) Pigs. Frontiers In Oncology 2019, 9: 9. PMID: 30723704, PMCID: PMC6349777, DOI: 10.3389/fonc.2019.00009.Peer-Reviewed Original ResearchPreclinical animal modelsSCID pigsOvarian carcinomaAnimal modelsEar tissueLate-stage diseaseLethal gynecologic malignancyOvarian cancer researchImmunodeficient pigsGynecologic malignanciesCarcinoma cell linesImmunohistochemical phenotypeCytokeratin 7Ovarian cancerXenotransplantation modelNeck musclesOrthotopic modelTumor massOvCa cellsPapillary carcinoma cell lineCarcinomaControl pigsClaudin-4Claudin-3Tumors
2018
Mutational landscape of primary, metastatic, and recurrent ovarian cancer reveals c-MYC gains as potential target for BET inhibitors
Li C, Bonazzoli E, Bellone S, Choi J, Dong W, Menderes G, Altwerger G, Han C, Manzano A, Bianchi A, Pettinella F, Manara P, Lopez S, Yadav G, Riccio F, Zammataro L, Zeybek B, Yang-Hartwich Y, Buza N, Hui P, Wong S, Ravaggi A, Bignotti E, Romani C, Todeschini P, Zanotti L, Zizioli V, Odicino F, Pecorelli S, Ardighieri L, Silasi DA, Litkouhi B, Ratner E, Azodi M, Huang GS, Schwartz PE, Lifton RP, Schlessinger J, Santin AD. Mutational landscape of primary, metastatic, and recurrent ovarian cancer reveals c-MYC gains as potential target for BET inhibitors. Proceedings Of The National Academy Of Sciences Of The United States Of America 2018, 116: 619-624. PMID: 30584090, PMCID: PMC6329978, DOI: 10.1073/pnas.1814027116.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsAzepinesBRCA1 ProteinBRCA2 ProteinCell Line, TumorClass I Phosphatidylinositol 3-KinasesFemaleHumansMiceMutationNeoplasm MetastasisNeoplasm Recurrence, LocalOvarian NeoplasmsProteinsProto-Oncogene Proteins c-mycTriazolesTumor Suppressor Protein p53Xenograft Model Antitumor AssaysConceptsOvarian cancerWhole-exome sequencingC-myc amplificationRecurrent tumorsPrimary tumorBET inhibitorsChemotherapy-resistant diseaseRecurrent ovarian cancerLethal gynecologic malignancyBilateral ovarian cancerChemotherapy-resistant tumorsPrimary metastatic tumorsMutational landscapeSomatic mutationsFresh-frozen tumorsGynecologic malignanciesMetastatic tumorsPrimary cell linesC-MYC gainPIK3CA amplificationTranscoelomic metastasisTherapeutic targetPatientsMetastatic abilityTumorsA novel multiple biomarker panel for the early detection of high-grade serous ovarian carcinoma
Han C, Bellone S, Siegel ER, Altwerger G, Menderes G, Bonazzoli E, Egawa-Takata T, Pettinella F, Bianchi A, Riccio F, Zammataro L, Yadav G, Marto JA, Penet MF, Levine DA, Drapkin R, Patel A, Litkouhi B, Ratner E, Silasi DA, Huang GS, Azodi M, Schwartz PE, Santin AD. A novel multiple biomarker panel for the early detection of high-grade serous ovarian carcinoma. Gynecologic Oncology 2018, 149: 585-591. PMID: 29572027, PMCID: PMC5986604, DOI: 10.1016/j.ygyno.2018.03.050.Peer-Reviewed Original ResearchConceptsHigh-grade serous ovarian carcinomaSerous ovarian carcinomaIL-6Ovarian cancerOvarian carcinomaE-cadHigh-grade serous ovarian adenocarcinomaEarly-stage ovarian cancerROC analysisEarly detectionMajority of patientsLethal gynecologic malignancyStage ovarian cancerOvarian cancer patientsBenign gynecologic pathologyNon-cancer controlsSerous ovarian adenocarcinomaEffective cancer screeningSerous ovarian cancerMultiple biomarker panelsFour-marker panelHigh differential gene expressionGynecologic malignanciesCA 125IL-1ra