2021
Immunotherapy in Cervical Cancer
Mauricio D, Zeybek B, Tymon-Rosario J, Harold J, Santin AD. Immunotherapy in Cervical Cancer. Current Oncology Reports 2021, 23: 61. PMID: 33852056, DOI: 10.1007/s11912-021-01052-8.Peer-Reviewed Original ResearchConceptsCervical cancerDifferent immune checkpoint inhibitorsPlatinum-based chemotherapy regimenTumor-infiltrating T lymphocytesPoly adenosine diphosphate ribose polymerase inhibitorsImmune checkpoint inhibitorsCombination therapy trialsCervical cancer patientsPositive cervical cancerNovel therapeutic modalitiesRibose polymerase inhibitorsAntibody-drug conjugatesCheckpoint inhibitorsChemotherapy regimenImmunotherapy studiesTherapeutic vaccinesInvestigative treatmentCancer patientsChemotherapy treatmentT lymphocytesTherapeutic modalitiesRecent FindingsThereTumor angiogenesis inhibitorTherapy trialsAngiogenesis inhibitorsIntegrated mutational landscape analysis of uterine leiomyosarcomas
Choi J, Manzano A, Dong W, Bellone S, Bonazzoli E, Zammataro L, Yao X, Deshpande A, Zaidi S, Guglielmi A, Gnutti B, Nagarkatti N, Tymon-Rosario JR, Harold J, Mauricio D, Zeybek B, Menderes G, Altwerger G, Jeong K, Zhao S, Buza N, Hui P, Ravaggi A, Bignotti E, Romani C, Todeschini P, Zanotti L, Odicino F, Pecorelli S, Ardighieri L, Bilguvar K, Quick CM, Silasi DA, Huang GS, Andikyan V, Clark M, Ratner E, Azodi M, Imielinski M, Schwartz PE, Alexandrov LB, Lifton RP, Schlessinger J, Santin AD. Integrated mutational landscape analysis of uterine leiomyosarcomas. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2025182118. PMID: 33876771, PMCID: PMC8053980, DOI: 10.1073/pnas.2025182118.Peer-Reviewed Original ResearchConceptsHomologous recombination DNA repair deficiencySequencing dataWhole-genome sequencing dataRNA sequencing dataTCGA samplesCopy number variation analysisATRX/DAXXCopy number lossNumber variation analysisDNA repair deficiencyWhole-exome sequencing dataRecurrent somatic mutationsCopy number gainsCancer Genome AtlasPatient-derived xenograftsTumor suppressorAkt geneGenetic landscapeHRD signaturesPTEN geneGenesMost fusionsC-MycMutational signaturesC-myc/
2020
Uterine serous carcinoma: Molecular features, clinical management, and new and future therapies
Lee EK, Fader AN, Santin AD, Liu JF. Uterine serous carcinoma: Molecular features, clinical management, and new and future therapies. Gynecologic Oncology 2020, 160: 322-332. PMID: 33160694, DOI: 10.1016/j.ygyno.2020.10.017.Peer-Reviewed Original ResearchConceptsUterine serous carcinomaMolecular featuresDistant recurrenceExtrauterine spreadMultimodality treatmentEndometrial cancerPoor prognosisSerous carcinomaAggressive subtypeClinical managementNovel therapiesFuture therapiesCurrent managementTherapyKey molecular featuresChemotherapySurgeryCarcinomaPrognosisRecurrenceRadiotherapyCancerSubtypesTargeting 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
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-38HER2 testing of gynecologic carcinosarcomas: tumor stratification for potential targeted therapy
Rottmann D, Snir OL, Wu X, Wong S, Hui P, Santin AD, Buza N. HER2 testing of gynecologic carcinosarcomas: tumor stratification for potential targeted therapy. Modern Pathology 2019, 33: 118-127. PMID: 31477811, DOI: 10.1038/s41379-019-0358-x.Peer-Reviewed Original ResearchMeSH KeywordsAgedAged, 80 and overBiomarkers, TumorCarcinosarcomaFallopian Tube NeoplasmsFemaleGene AmplificationHumansMiddle AgedMolecular Targeted TherapyReceptor, ErbB-2Uterine NeoplasmsConceptsEndometrial serous carcinomaHER2-positive tumorsSerous carcinomaSarcoma componentHER2 statusGynecologic carcinosarcomaHER2 expression/amplificationRecent phase II clinical trialPhase II clinical trialCarboplatin-paclitaxel chemotherapyEquivocal HER2 expressionProgression-free survivalAppropriate patient selectionExpression/amplificationFemale genital tractMembranous staining patternHER2 protein expressionHER2 immunohistochemical scoresUterine primaryDismal prognosisPatient selectionCarcinoma componentMixed carcinomasHER2 expressionClinical trialsPrevalence and role of HER2 mutations in cancer
Cocco E, Lopez S, Santin AD, Scaltriti M. Prevalence and role of HER2 mutations in cancer. Pharmacology & Therapeutics 2019, 199: 188-196. PMID: 30951733, PMCID: PMC6571037, DOI: 10.1016/j.pharmthera.2019.03.010.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBreast NeoplasmsDrug Resistance, NeoplasmHumansMolecular Targeted TherapyMutationReceptor, ErbB-2ConceptsHER2 mutationsCell-free DNARecent clinical trialsNext-generation sequencingActivity of HER2Variety of tumorsPreclinical dataClinical trialsDifferent human cancersTumor biopsiesOncogenic driversClinical settingCancer typesHER2Human cancersTherapyCancerPrevalenceVariable sensitivityGeneration sequencingMutationsBiological characterizationBiopsyClinicTumors
2018
Mechanisms of resistance to HER2-targeted therapies in HER2-amplified uterine serous carcinoma, and strategies to overcome it.
Menderes G, Lopez S, Han C, Altwerger G, Gysler S, Varughese J, Schwartz PE, Santin AD. Mechanisms of resistance to HER2-targeted therapies in HER2-amplified uterine serous carcinoma, and strategies to overcome it. Discovery Medicine 2018, 26: 39-50. PMID: 30265854.Peer-Reviewed Original ResearchMeSH KeywordsCystadenocarcinoma, SerousDrug Resistance, NeoplasmFemaleHumansMolecular Targeted TherapyOncogenesReceptor, ErbB-2Uterine NeoplasmsConceptsUterine serous carcinomaTyrosine kinase inhibitorsUSC patientsSerous carcinomaHER2/neu-targeted therapiesEndometrial cancer-related deathsHER2/neu amplificationKinase inhibitorsSingle-agent trastuzumabSignificant clinical activityRecent whole-exome sequencing studiesCancer-related deathEffective therapeutic strategyTumor growth inhibitionEndometrial cancerAggressive subtypeMechanisms of resistanceWhole-exome sequencing studiesClinical activityPreclinical studiesTarget therapyTherapeutic strategiesNeu amplificationHER2TherapyExceptional Response to Pembrolizumab in a Metastatic, Chemotherapy/Radiation-Resistant Ovarian Cancer Patient Harboring a PD-L1-Genetic Rearrangement
Bellone S, Buza N, Choi J, Zammataro L, Gay L, Elvin J, Rimm DL, Liu Y, Ratner E, Schwartz PE, Santin AD. Exceptional Response to Pembrolizumab in a Metastatic, Chemotherapy/Radiation-Resistant Ovarian Cancer Patient Harboring a PD-L1-Genetic Rearrangement. Clinical Cancer Research 2018, 24: 3282-3291. PMID: 29351920, PMCID: PMC6050068, DOI: 10.1158/1078-0432.ccr-17-1805.Peer-Reviewed Original ResearchMeSH KeywordsAged, 80 and overAntibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalB7-H1 AntigenBiomarkers, TumorBiopsyComputational BiologyDrug Resistance, NeoplasmExome SequencingFemaleGene RearrangementHLA AntigensHumansMolecular Targeted TherapyMutationOvarian NeoplasmsPositron Emission Tomography Computed TomographyProgrammed Cell Death 1 ReceptorReceptors, Cell SurfaceRetreatmentT-LymphocytesTreatment OutcomeConceptsImmune checkpoint inhibitor pembrolizumabCheckpoint inhibitor pembrolizumabComplete clinical responseClinical responsePD-L1Ovarian carcinomaAberrant PD-L1 expressionPD-L1 surface expressionAnti-PD1 inhibitorsPD-L1 expressionRemarkable clinical responsesHigh-grade ovarian carcinomaStandard treatment modalityAlternative therapeutic optionClear cell featuresNovel treatment optionsSignificant side effectsT-cell lymphocytesWhole exome sequencing techniqueClin Cancer ResMetastatic human tumorsRecurrent diseaseComplete responseHeavy infiltrationTherapeutic optionsNovel targeted therapies in ovarian and uterine carcinosarcomas.
Han C, Altwerger G, Menderes G, Haines K, Feinberg J, Lopez S, Manzano A, Varughese J, Santin AD. Novel targeted therapies in ovarian and uterine carcinosarcomas. Discovery Medicine 2018, 25: 309-319. PMID: 30021104.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarcinosarcomaFemaleHumansMolecular Targeted TherapyNeoplasm ProteinsOvarian NeoplasmsUterine NeoplasmsConceptsMultiple genes/pathwaysPI3K/Akt/mTORFemale genital tractEffective treatment strategiesUnmet medical needAkt/mTORGynecologic tumorsPoor prognosisUterine carcinosarcomaAggressive tumorsTreatment modalitiesBiphasic tumorWhole-exome sequencing studiesGenital tractTreatment strategiesCarcinomatous componentCarcinosarcomaMedical needAberrant activationTumorsGenes/pathwaysCell cycle regulationGenetic landscapeSequencing studiesPrognosis
2016
Novel targeted therapies in uterine serous carcinoma, an aggressive variant of endometrial cancer.
Menderes G, Clark M, Santin AD. Novel targeted therapies in uterine serous carcinoma, an aggressive variant of endometrial cancer. Discovery Medicine 2016, 21: 293-303. PMID: 27232515.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalAntineoplastic AgentsClass I Phosphatidylinositol 3-KinasesCyclin ECystadenocarcinoma, SerousEndometrial NeoplasmsEpothilonesExomeFemaleHumansMolecular Targeted TherapyMutationNeoplasm Recurrence, LocalOncogene ProteinsPrognosisProtein Kinase InhibitorsProtein Phosphatase 2RadioimmunotherapyReceptor, ErbB-2Sequence Analysis, DNASignal TransductionTOR Serine-Threonine KinasesTubulin ModulatorsTumor Suppressor Protein p53Uterine NeoplasmsVascular Endothelial Growth Factor AConceptsUterine serous carcinomaEndometrial cancerSerous carcinomaTreatment of USCPIK3CA/AKT/mTOREndometrial cancer casesRecent whole-exome sequencing studiesHER2/neu geneNovel therapeutic targetAkt/mTORBiologic therapyAggressive variantDismal prognosisAggressive subtypeWhole-exome sequencing studiesCancer casesTherapeutic targetSubsequent deathDriver mutationsNeu geneGain of functionCarcinomaTherapyCancerSequencing studies
2015
An update on the current pharmacotherapy for endometrial cancer
de Haydu C, Black JD, Schwab CL, English DP, Santin AD. An update on the current pharmacotherapy for endometrial cancer. Expert Opinion On Pharmacotherapy 2015, 17: 489-499. PMID: 26629895, DOI: 10.1517/14656566.2016.1127351.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic AgentsAntineoplastic Agents, HormonalChemotherapy, AdjuvantEndometrial NeoplasmsFemaleHumansMolecular Targeted TherapyConceptsEndometrial cancerMainstay of treatmentCommon gynecologic malignancyCurrent conventional therapiesGynecologic malignanciesCurrent pharmacotherapyAvailable pharmacotherapiesConventional therapyCurrent therapiesEndometrial tumorsTargeted therapyImmunohistochemical characterizationRadiation therapyClinical careAggressive formNew therapiesPreclinical settingTherapyTherapeutic agentsCancerPharmacotherapyTumorsAvailable literatureHistoric treatmentTreatmentImmunotherapy and targeted therapy for cervical cancer: an update
Menderes G, Black J, Schwab CL, Santin AD. Immunotherapy and targeted therapy for cervical cancer: an update. Expert Review Of Anticancer Therapy 2015, 16: 83-98. PMID: 26568261, DOI: 10.1586/14737140.2016.1121108.Peer-Reviewed Original ResearchConceptsCervical cancer patientsCervical cancerCancer patientsImmune check pointsUse of immunotherapyMetastatic cervical cancerPrognosis of patientsActionable driver mutationsTyrosine kinase inhibitorsImmune system interactionsImmunotherapy studiesMedian survivalAngiogenesis inhibitorsChemotherapeutic drugsPatientsDriver mutationsKinase inhibitorsNew therapeuticsCancerNext-generation sequencingImmunotherapyTherapyGeneration sequencingInhibitorsPrognosisTargeted therapy in the treatment of uterine serous carcinoma
Schwab CL, Santin AD. Targeted therapy in the treatment of uterine serous carcinoma. Pharmacogenomics 2015, 16: 97-99. PMID: 25616096, DOI: 10.2217/pgs.14.176.Peer-Reviewed Original Research
2014
Past, present and future targets for immunotherapy in ovarian cancer
Schwab CL, English DP, Roque DM, Pasternak M, Santin AD. Past, present and future targets for immunotherapy in ovarian cancer. Immunotherapy 2014, 6: 1279-1293. PMID: 25524384, PMCID: PMC4312614, DOI: 10.2217/imt.14.90.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsClinical Trials as TopicFemaleHumansImmunomodulationImmunotherapyLymphocyte ActivationMolecular Targeted TherapyOvarian NeoplasmsRecurrenceConceptsOvarian cancerImmune systemGoal of immunotherapyOvarian cancer immunotherapyConventional cytotoxic chemotherapyCause of deathAdvanced surgical techniquesDifferent immunotherapiesTremendous toxicityCytotoxic chemotherapyGynecologic malignanciesDisease recurrenceMicroscopic diseaseCancer immunotherapyImmune modulationSurgical techniqueCurrent evidenceImmunotherapyCurrent ongoing studiesCancerRecurrenceOngoing studiesFuture targetsChemotherapyMalignancyTargeted Therapy in Uterine Serous Carcinoma: An Aggressive Variant of Endometrial Cancer
Black JD, English DP, Roque DM, Santin AD. Targeted Therapy in Uterine Serous Carcinoma: An Aggressive Variant of Endometrial Cancer. Women's Health 2014, 10: 45-57. PMID: 24328598, PMCID: PMC3984476, DOI: 10.2217/whe.13.72.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic AgentsClass I Phosphatidylinositol 3-KinasesCyclin ECystadenocarcinoma, SerousDrug Resistance, NeoplasmFemaleGenes, erbB-2HumansMolecular Targeted TherapyMutationNeoplasm Recurrence, LocalNeoplasm StagingPhosphatidylinositol 3-KinasesRandomized Controlled Trials as TopicUterine NeoplasmsConceptsUterine serous carcinomaEndometrial cancerAggressive variantSerous carcinomaRecurrent uterine serous carcinomaPIK3CA/AKT/mTORComprehensive surgical stagingRecent whole-exome sequencing studiesHER2/neu geneVaginal cuff brachytherapyNovel therapeutic targetAkt/mTORUSC therapyPaclitaxel chemotherapySurgical stagingBiologic therapyTargeted therapyWhole-exome sequencing studiesTherapeutic targetDriver mutationsTherapyNeu geneCancerGain of functionCarcinoma
2013
Class III b-tubulin overexpression in gynecologic tumors: implications for the choice of microtubule targeted agents?
English DP, Roque DM, Santin AD. Class III b-tubulin overexpression in gynecologic tumors: implications for the choice of microtubule targeted agents? Expert Review Of Anticancer Therapy 2013, 13: 63-74. PMID: 23259428, DOI: 10.1586/era.12.158.Peer-Reviewed Original Research
2012
Development of targeted therapy in uterine serous carcinoma, a biologically aggressive variant of endometrial cancer
El-Sahwi KS, Schwartz PE, Santin AD. Development of targeted therapy in uterine serous carcinoma, a biologically aggressive variant of endometrial cancer. Expert Review Of Anticancer Therapy 2012, 12: 41-49. PMID: 22149431, PMCID: PMC3287395, DOI: 10.1586/era.11.192.Peer-Reviewed Original ResearchConceptsType II endometrial cancerUterine serous cancerEndometrial cancerSerous cancerAggressive variantType I endometrial cancerFemale genital malignanciesUterine serous carcinomaOlder patientsGenital malignanciesMost recurrencesBetter prognosisSerous carcinomaEndometrial tumorsAggressive subsetEarly diagnosisTherapeutic markersMost carcinomasCancerCarcinomaMarkersHypertensionPostmenopausalObesityPatients
2011
Expression of Tissue factor in Adenocarcinoma and Squamous Cell Carcinoma of the Uterine Cervix: Implications for immunotherapy with hI-con1, a factor VII-IgGFcchimeric protein targeting tissue factor
Cocco E, Varughese J, Buza N, Bellone S, Glasgow M, Bellone M, Todeschini P, Carrara L, Silasi DA, Azodi M, Schwartz PE, Rutherford TJ, Pecorelli S, Lockwood CJ, Santin AD. Expression of Tissue factor in Adenocarcinoma and Squamous Cell Carcinoma of the Uterine Cervix: Implications for immunotherapy with hI-con1, a factor VII-IgGFcchimeric protein targeting tissue factor. BMC Cancer 2011, 11: 263. PMID: 21693061, PMCID: PMC3141777, DOI: 10.1186/1471-2407-11-263.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaCarcinoma, Squamous CellCell Line, TumorComplement System ProteinsCytotoxicity Tests, ImmunologicDrug Screening Assays, AntitumorFemaleHuman papillomavirus 16Human papillomavirus 18HumansImmunoconjugatesImmunoglobulin GImmunotherapyInterleukin-2KeratinocytesMolecular Targeted TherapyNeoplasm ProteinsNeovascularization, PathologicPapillomavirus InfectionsRNA, MessengerRNA, NeoplasmThromboplastinUterine Cervical NeoplasmsConceptsCervical cancer cell linesPrimary cervical cancer cell linesCervical carcinoma cell linesCancer cell linesCervical cancerCarcinoma cell linesFactor VII/VIIaTissue factorUterine cervixCell linesImportant worldwide health problemTargeting tissue factorStandard treatment modalitySquamous cell carcinomaExpression of TFWorldwide health problemNovel therapeutic agentsNormal cervical keratinocytesAdenocarcinoma histologyBackgroundCervical cancerCancer refractoryRecurrent diseaseCell carcinomaTreatment modalitiesNovel therapiesHigh-grade, chemotherapy-resistant primary ovarian carcinoma cell lines 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, Bellone M, Todeschini P, Carrara L, Schwartz PE, Rutherford TJ, Pecorelli S, Santin AD. High-grade, chemotherapy-resistant primary ovarian carcinoma cell lines overexpress human trophoblast cell-surface marker (Trop-2) and are highly sensitive to immunotherapy with hRS7, a humanized monoclonal anti-Trop-2 antibody. Gynecologic Oncology 2011, 122: 171-177. PMID: 21453957, PMCID: PMC3104081, DOI: 10.1016/j.ygyno.2011.03.002.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalAntibody-Dependent Cell CytotoxicityAntigens, NeoplasmCell Adhesion MoleculesCell Line, TumorDrug Resistance, NeoplasmFemaleFlow CytometryHumansImmunoglobulin GImmunohistochemistryInterleukin-2Killer Cells, NaturalMiddle AgedMolecular Targeted TherapyOvarian NeoplasmsRNA, MessengerConceptsAntibody-dependent cellular cytotoxicityOvarian cancer cell linesTrop-2 expressionAnti-Trop-2 antibodyChemotherapy-resistant ovarian cancerPrimary ovarian cancer cell linesCancer cell linesOvarian carcinoma cell linesInterleukin-2Cell surface markersCarcinoma cell linesOvarian cancerCell linesTrop-2Therapeutic agentsChemotherapy-resistant diseaseNovel therapeutic agentsEffect of serumOvarian diseaseControl antibodyHRS7Real-time PCRCellular cytotoxicityCarcinoma specimensRelease assays