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 deliveryDeliveryChapter 3 Ovarian carcinosarcoma
Tymon-Rosario J, Chui M, Santin A. Chapter 3 Ovarian carcinosarcoma. 2023, 41-54. DOI: 10.1016/b978-0-323-82938-0.00003-3.Peer-Reviewed Original ResearchHigh-grade serous ovarian carcinomaSurvival of womenEpithelial ovarian cancerSerous ovarian carcinomaEpithelial-mesenchymal transitionCarcinosarcoma patientsGynecologic tractHistologic subtypeOvarian carcinosarcomaAggressive diseaseAggressive malignancyCarcinoma componentOvarian tumorsClinical managementOvarian carcinomaClinical trialsOvarian cancerSarcomatous elementsAggressive natureCarcinosarcomaTumorsDiseaseSurvivalMolecular studiesPatients
2021
Vessel-Targeting Nanoclovers Enable Noninvasive Delivery of Magnetic Hyperthermia–Chemotherapy Combination for Brain Cancer Treatment
Liu F, Wu H, Peng B, Zhang S, Ma J, Deng G, Zou P, Liu J, Chen AT, Li D, Bellone S, Santin AD, Moliterno J, Zhou J. Vessel-Targeting Nanoclovers Enable Noninvasive Delivery of Magnetic Hyperthermia–Chemotherapy Combination for Brain Cancer Treatment. Nano Letters 2021, 21: 8111-8118. PMID: 34597054, DOI: 10.1021/acs.nanolett.1c02459.Peer-Reviewed Original ResearchConceptsBrain cancer treatmentSystemic chemotherapyCancer treatmentBrain cancer developmentNoninvasive deliverySystemic drug deliveryIntravenous administrationBrain tumorsIntracranial injectionBrain cancerTumor vasculatureCancer developmentImproved efficacyTumor cellsImproved treatmentMagnetic field exposureChemotherapyClinical applicationTumorsNoninvasive natureTreatmentDeliveryHyperthermiaField exposureCancer
2020
Modeling biological and genetic diversity in upper tract urothelial carcinoma with patient derived xenografts
Kim K, Hu W, Audenet F, Almassi N, Hanrahan AJ, Murray K, Bagrodia A, Wong N, Clinton TN, Dason S, Mohan V, Jebiwott S, Nagar K, Gao J, Penson A, Hughes C, Gordon B, Chen Z, Dong Y, Watson PA, Alvim R, Elzein A, Gao SP, Cocco E, Santin AD, Ostrovnaya I, Hsieh JJ, Sagi I, Pietzak EJ, Hakimi AA, Rosenberg JE, Iyer G, Vargas HA, Scaltriti M, Al-Ahmadie H, Solit DB, Coleman JA. Modeling biological and genetic diversity in upper tract urothelial carcinoma with patient derived xenografts. Nature Communications 2020, 11: 1975. PMID: 32332851, PMCID: PMC7181640, DOI: 10.1038/s41467-020-15885-7.Peer-Reviewed Original ResearchMeSH KeywordsAgedAnimalsAntibodies, Monoclonal, HumanizedAntineoplastic AgentsBiopsyCamptothecinCarcinoma, Transitional CellFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticGenetic VariationHigh-Throughput Nucleotide SequencingHumansImmunoconjugatesInterleukin Receptor Common gamma SubunitMaleMiceMice, Inbred NODMice, SCIDMiddle AgedMutationNeoplasm MetastasisNeoplasm TransplantationPhenotypePrecision MedicineProspective StudiesQuinolinesRetrospective StudiesSequence Analysis, RNATrastuzumabUrinary Bladder NeoplasmsUrotheliumConceptsUpper tract urothelial carcinomaUrothelial carcinomaCorresponding patient tumorsEstablishment of patientHigh genomic concordancePersonalized medicine strategiesHER2 kinase inhibitorDisease-specific modelsUTUC patientsCell line modelsPDX modelsBladder cancerTreatment paradigmGenomic concordanceInvasive tumorsSuperior efficacyPatient tumorsPatientsKinase inhibitorsAntibody drugsMedicine strategiesBiological heterogeneityCarcinomaXenograftsTumors
2019
Prevalence 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 ResearchConceptsHER2 mutationsCell-free DNARecent clinical trialsNext-generation sequencingActivity of HER2Variety of tumorsPreclinical dataClinical trialsDifferent human cancersTumor biopsiesOncogenic driversClinical settingCancer typesHER2Human cancersTherapyCancerPrevalenceVariable sensitivityGeneration sequencingMutationsBiological characterizationBiopsyClinicTumorsHuman 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 abilityTumorsNovel 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 ResearchConceptsMultiple 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 studiesPrognosisClaudin3 is localized outside the tight junctions in human carcinomas
Corsini M, Ravaggi A, Odicino F, Santin AD, Ravelli C, Presta M, Romani C, Mitola S. Claudin3 is localized outside the tight junctions in human carcinomas. Oncotarget 2018, 9: 18446-18453. PMID: 29719617, PMCID: PMC5915084, DOI: 10.18632/oncotarget.24858.Peer-Reviewed Original ResearchExpression of Claudin3Tight junction proteinsTight junctionsEpithelial-derived tumorsProstate carcinomaOncomine databaseClaudin3Tumor samplesCBioPortal databaseTumoral tissueGene alterationsHuman carcinomasTherapeutic drugsTissue samplesJunction proteinsNovel diagnostic probesHealthy tissueImmunofluorescence analysisCarcinomaTumorsNumber alterationsTissueAlterationsSurgeryBladder
2016
Regression 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 mutationsNivolumabChemotherapyPolymerase ε (POLE) ultra-mutation in uterine tumors correlates with T lymphocyte infiltration and increased resistance to platinum-based chemotherapy in vitro
Bellone S, Bignotti E, Lonardi S, Ferrari F, Centritto F, Masserdotti A, Pettinella F, Black J, Menderes G, Altwerger G, Hui P, Lopez S, de Haydu C, Bonazzoli E, Predolini F, Zammataro L, Cocco E, Ferrari F, Ravaggi A, Romani C, Facchetti F, Sartori E, Odicino FE, Silasi DA, Litkouhi B, Ratner E, Azodi M, Schwartz PE, Santin AD. Polymerase ε (POLE) ultra-mutation in uterine tumors correlates with T lymphocyte infiltration and increased resistance to platinum-based chemotherapy in vitro. Gynecologic Oncology 2016, 144: 146-152. PMID: 27894751, PMCID: PMC5183545, DOI: 10.1016/j.ygyno.2016.11.023.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic AgentsCarboplatinCarcinomaCD4 Lymphocyte CountCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCell SurvivalDisease-Free SurvivalDNA Polymerase IIDrug Resistance, NeoplasmEndometrial NeoplasmsFemaleHumansMicrosatellite InstabilityMiddle AgedMutationPoly-ADP-Ribose Binding ProteinsTumor Cells, CulturedConceptsBetter prognosisTumor cell linesInfiltration of CD4Number of CD4Platinum-based chemotherapyT lymphocyte infiltrationPD-1 receptorCell linesLow metastatic capabilityPOLE-mutated tumorsWild-type ECsEC cell linesLymphocyte infiltrationFavorable prognosisPD-1EC patientsType tumorsEnhanced immunogenicityT lymphocytesMolecular subtypesTumors correlatesChemotherapyMetastatic capabilityPrognosisTumors
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 ResearchConceptsEndometrial cancerMainstay of treatmentCommon gynecologic malignancyCurrent conventional therapiesGynecologic malignanciesCurrent pharmacotherapyAvailable pharmacotherapiesConventional therapyCurrent therapiesEndometrial tumorsTargeted therapyImmunohistochemical characterizationRadiation therapyClinical careAggressive formNew therapiesPreclinical settingTherapyTherapeutic agentsCancerPharmacotherapyTumorsAvailable literatureHistoric treatmentTreatmentManagement of Borderline Ovarian Tumors Based on Patient and Tumor Characteristics
Black JD, Altwerger GH, Ratner E, Lu L, Silasi DA, Azodi M, Santin AD, Schwartz PE, Rutherford TJ. Management of Borderline Ovarian Tumors Based on Patient and Tumor Characteristics. Gynecologic And Obstetric Investigation 2015, 81: 169-173. PMID: 26067608, DOI: 10.1159/000431219.Peer-Reviewed Original ResearchMucinous tumorsSeromucinous tumorsOvarian tumorsComplete surgical stagingNormal-appearing appendixBorderline ovarian tumorsLymph node involvementRetrospective cohort analysisRisk of recurrenceAggressive stagingNodal diseaseSurgical stagingHazard ratioNode involvementDisease recurrencePseudomyxoma peritoneiSerous tumorsSingle institutionPathology reportsCohort analysisLower riskRecurrenceMultivariate analysisFrozen sectionsTumorsClostridium Perfringens Enterotoxin (CPE) and CPE-Binding Domain (c-CPE) for the Detection and Treatment of Gynecologic Cancers
Black JD, Lopez S, Cocco E, Schwab CL, English DP, Santin AD. Clostridium Perfringens Enterotoxin (CPE) and CPE-Binding Domain (c-CPE) for the Detection and Treatment of Gynecologic Cancers. Toxins 2015, 7: 1116-1125. PMID: 25835384, PMCID: PMC4417958, DOI: 10.3390/toxins7041116.Peer-Reviewed Original ResearchConceptsClostridium perfringens enterotoxinClaudin-3Claudin-4Perfringens enterotoxinAggressive human cancer cellsGynecologic malignanciesGynecologic cancerHuman cancer cellsOperative settingHuman tumorsCancer cellsPotential roleTumorsSurface proteinsEnterotoxinTreatmentHigh affinitySurgeryMalignancyCancerCytolysisReceptorsFuture Directions and New Targets in Endometrial Cancer
Black J, Roque D, Gold L, Santin A. Future Directions and New Targets in Endometrial Cancer. Current Clinical Oncology 2015, 259-271. DOI: 10.1007/7631_2015_1.Peer-Reviewed Original ResearchEndometrial cancerNext-generation sequencingPathway aberrationsMolecular aberrationsUnique molecular characteristicsCancerNew targetsSomatic mutationsTherapyHeterogeneous somatic mutationsMolecular characteristicsCompelling evidenceGeneration sequencingRecent advancesProper classificationAberrationsTumorsDisease
2013
Claudins Overexpression in Ovarian Cancer: Potential Targets for Clostridium Perfringens Enterotoxin (CPE) Based Diagnosis and Therapy
English DP, Santin AD. Claudins Overexpression in Ovarian Cancer: Potential Targets for Clostridium Perfringens Enterotoxin (CPE) Based Diagnosis and Therapy. International Journal Of Molecular Sciences 2013, 14: 10412-10437. PMID: 23685873, PMCID: PMC3676847, DOI: 10.3390/ijms140510412.Peer-Reviewed Original ResearchConceptsClostridium perfringens enterotoxinOvarian cancerClaudin-3Chemotherapy-resistant ovarian cancerPerfringens enterotoxinAggressive solid tumorsTight junction proteinsMalignant human tissuesPotent cytolytic toxinClaudin overexpressionOvarian tumorsSolid tumorsClaudin-4CancerJunction proteinsParacellular permeabilityPotential targetExact roleTumorsAttractive targetHuman tissuesSurface proteinsCytolytic toxinEnterotoxinClaudin family
2012
In vitro chemosensitivity assay for patients with gynecologic sarcoma.
Santin A, Varughese J, Chan J, McClure C, Lea J. In vitro chemosensitivity assay for patients with gynecologic sarcoma. Journal Of Clinical Oncology 2012, 30: e13078-e13078. DOI: 10.1200/jco.2012.30.15_suppl.e13078.Peer-Reviewed Original ResearchAntigen-specific immunotherapy for ovarian cancer
Roque D, Santin A. Antigen-specific immunotherapy for ovarian cancer. 2012, 136-154. DOI: 10.2217/ebo.11.180.Peer-Reviewed Original ResearchOvarian cancer immunotherapyAntigen-specific immunotherapyTumor-associated antigensCancer immunotherapyOvarian tumor-associated antigensSpecific T cell responsesCritical immune checkpointsRegulatory T cellsT cell responsesOvarian cancer pathogenesisB7 family proteinsImmune checkpointsClinical trialsOvarian cancerT cellsImmune responseSuccessful therapyInhibitory pathwaysImmune evasionImmunotherapySpecific antigenHost defenseCancer pathogenesisAntigenTumors
2002
Novel target antigens for dendritic cell-based immunotherapy against ovarian cancer
Cannon MJ, O’Brien T, Underwood LJ, Crew MD, Bondurant KL, Santin AD. Novel target antigens for dendritic cell-based immunotherapy against ovarian cancer. Expert Review Of Anticancer Therapy 2002, 2: 97-105. PMID: 12113075, DOI: 10.1586/14737140.2.1.97.Peer-Reviewed Original ResearchConceptsDendritic cell-based immunotherapyCell-based immunotherapyPowerful antigen-presenting cellsPrimary T cell responsesDendritic cell vaccinationT cell responsesOvarian tumor antigenTumor-specific target antigensAntigen-presenting cellsTumor-specific antigensEffective immune responseCell vaccinationDendritic cellsMalignant diseaseOvarian cancerImmune responseTumor antigensTarget antigenImmunotherapyAntigenNovel targetVaccinationRecent recognitionCellsTumors
1996
Differential Effects of High-Dose Gamma Irradiation on the Production of Transforming Growth Factor-Beta in Fresh and Established Human Ovarian Cancer
Santin A, Hiserodt J, DiSaia P, Pecorelli S, Granger G. Differential Effects of High-Dose Gamma Irradiation on the Production of Transforming Growth Factor-Beta in Fresh and Established Human Ovarian Cancer. Gynecologic Oncology 1996, 61: 403-408. PMID: 8641623, DOI: 10.1006/gyno.1996.0164.Peer-Reviewed Original ResearchConceptsOvarian carcinoma cell linesCarcinoma cell linesOvarian tumorsFresh tumorsCell linesHigh dosesImmunoinhibitory cytokinesTumor cellsFresh ovarian tumorsTGF-beta secretionTGF-beta productionCytokines TNF-alphaFresh tumor cellsWeak immunological responseFresh tumor samplesHuman ovarian cancerHuman ovarian carcinoma cell linesTNF-alphaOvarian cancerImmunological responseIFN-gammaCytokinesTumorsTumor samplesContinuous cell lines