2024
Microtubule-Targeting Agents: Disruption of the Cellular Cytoskeleton as a Backbone of Ovarian Cancer Therapy
Danziger M, Noble H, Roque D, Xu F, Rao G, Santin A. Microtubule-Targeting Agents: Disruption of the Cellular Cytoskeleton as a Backbone of Ovarian Cancer Therapy. Advances In Experimental Medicine And Biology 2024, 1452: 1-19. PMID: 38805122, DOI: 10.1007/978-3-031-58311-7_1.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsCytoskeletonDrug Resistance, NeoplasmFemaleHumansMicrotubulesOvarian NeoplasmsTubulin ModulatorsConceptsOvarian cancer therapyCancer therapyTargets of anti-cancer therapyIntracellular traffickingCellular processesCellular cytoskeletonMicrotubule-active agentsAnti-cancer therapyMicrotubule-stabilizing agentEffective regimenDynamic polymersDevelopment of resistanceB-tubulinTherapeutic challengeMicrotubulesRecurrent settingTherapyEukaryotesCytoskeletonMitosisHeterodimerMotilityTraffickingRegimensReplication
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 ResearchMeSH KeywordsAntibodies, MonoclonalAntineoplastic AgentsEpidermal Growth FactorFemaleGenital Neoplasms, FemaleHumansImmunoconjugatesReceptor, ErbB-2ConceptsHuman 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 deliveryDeliveryThe Poly (ADP-ribose) polymerase inhibitor olaparib and pan-ErbB inhibitor neratinib are highly synergistic in HER2 overexpressing epithelial ovarian carcinoma in vitro and in vivo
Han C, McNamara B, Bellone S, Harold J, Manara P, Hartwich T, Mutlu L, Yang-Hartwich Y, Zipponi M, Demirkiran C, Verzosa M, Altwerger G, Ratner E, Huang G, Clark M, Andikyan V, Azodi M, Dottino P, Schwartz P, Santin A. The Poly (ADP-ribose) polymerase inhibitor olaparib and pan-ErbB inhibitor neratinib are highly synergistic in HER2 overexpressing epithelial ovarian carcinoma in vitro and in vivo. Gynecologic Oncology 2023, 170: 172-178. PMID: 36706643, PMCID: PMC10023457, DOI: 10.1016/j.ygyno.2023.01.015.Peer-Reviewed Original ResearchConceptsCombination of olaparibOvarian cancerHER2 expressionSingle agentCell linesGynecologic cancer mortalityHER2-negative tumorsOvarian cancer cell linesOvarian cancer patientsEpithelial ovarian carcinomaNovel therapeutic optionsOC cell linesUnmet medical needPoly (ADP-ribose) polymerase (PARP) inhibitorsPan-ErbB inhibitorSingle-agent olaparibPolymerase inhibitor olaparibPoly (ADP-ribose) polymerase (PARP) inhibitor olaparibPrimary HER2Cancer cell linesNegative tumorsTherapeutic optionsCancer mortalityCancer patientsNeu expression
2022
Ovarian and uterine carcinosarcomas are sensitive in vitro and in vivo to elimusertib, a novel ataxia-telangiectasia and Rad3-related (ATR) kinase inhibitor
Manavella D, McNamara B, Harold J, Bellone S, Hartwich T, Yang-Hartwich Y, Mutlu L, Zipponi M, Demirkiran C, Verzosa M, Altwerger G, Ratner E, Huang G, Clark M, Andikyan V, Azodi M, Schwartz P, Dottino P, Choi J, Alexandrov L, Buza N, Hui P, Santin A. Ovarian and uterine carcinosarcomas are sensitive in vitro and in vivo to elimusertib, a novel ataxia-telangiectasia and Rad3-related (ATR) kinase inhibitor. Gynecologic Oncology 2022, 169: 98-105. PMID: 36525930, PMCID: PMC9925406, DOI: 10.1016/j.ygyno.2022.12.003.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsAtaxia TelangiectasiaAtaxia Telangiectasia Mutated ProteinsCarcinosarcomaCell Line, TumorFemaleHumansOvaryUterine NeoplasmsConceptsHomologous recombination deficiencyCS cell linesCell linesWestern blotKinase inhibitorsOverall animal survivalProtein expressionDose-dependent increaseDose-dependent inhibitionCarcinosarcoma cell lineTumor growth inhibitionCaspase-3 expressionEndometrioid histologyAggressive malignancyUterine carcinosarcomaCS patientsPreclinical activityClinical trialsEpithelial componentAnimal survivalXenograftsApoptosis markersRecombination deficiencyP-ATRP-Chk1Advances 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 ResearchMeSH KeywordsAntineoplastic AgentsFemaleGenital Neoplasms, FemaleHumansImmunoconjugatesNeoplasm Recurrence, LocalOvarian NeoplasmsConceptsAntibody-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 AdministrationTargeted Therapies in the Treatment of Uterine Serous Carcinoma
Tymon-Rosario J, Gorman M, Santin A. Targeted Therapies in the Treatment of Uterine Serous Carcinoma. Current Treatment Options In Oncology 2022, 23: 1804-1817. PMID: 36447064, DOI: 10.1007/s11864-022-01030-7.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic AgentsCystadenocarcinoma, SerousFemaleHumansImmunoconjugatesTrastuzumabUterine NeoplasmsConceptsUterine serous carcinomaRecurrent diseaseSerous carcinomaTreatment of USCEffective disease-modifying treatmentMolecular classificationAppropriate surgical stagingAddition of trastuzumabCombination of immunotherapySystemic adjuvant treatmentDisease-modifying treatmentsEnrollment of patientsHER2-positive tumorsTyrosine kinase inhibitorsUnmet medical needPersonalized cancer careAntibody-drug conjugatesOpinion statementDespiteSurgical cytoreductionAdjuvant treatmentSurgical stagingDismal prognosisSurvival outcomesTherapeutic optionsCancer care
2021
Integrated 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
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 heterogeneityCarcinomaXenograftsTumorsCervical 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
Sacituzumab Govitecan-hziy in Refractory Metastatic Triple-Negative Breast Cancer
Bardia A, Mayer IA, Vahdat LT, Tolaney SM, Isakoff SJ, Diamond JR, O'Shaughnessy J, Moroose RL, Santin AD, Abramson VG, Shah NC, Rugo HS, Goldenberg DM, Sweidan AM, Iannone R, Washkowitz S, Sharkey RM, Wegener WA, Kalinsky K. Sacituzumab Govitecan-hziy in Refractory Metastatic Triple-Negative Breast Cancer. New England Journal Of Medicine 2019, 380: 741-751. PMID: 30786188, DOI: 10.1056/nejmoa1814213.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAnemiaAntibodies, Monoclonal, HumanizedAntigens, NeoplasmAntineoplastic AgentsCamptothecinCell Adhesion MoleculesDiarrheaDose-Response Relationship, DrugFemaleHumansImmunoconjugatesInfusions, IntravenousIrinotecanMaleMiddle AgedNeutropeniaProgression-Free SurvivalSurvival RateTriple Negative Breast NeoplasmsConceptsMetastatic triple-negative breast cancerTriple-negative breast cancerSacituzumab govitecan-hziyProgression-free survivalClinical benefit rateIndependent central reviewBreast cancerResponse rateAdverse eventsOverall survivalCentral reviewBenefit rateHuman trophoblast cell surface antigen 2Refractory metastatic triple-negative breast cancerTrophoblast cell surface antigen 2Median progression-free survivalSN-38Shorter progression-free survivalCell surface antigen 2Blinded independent central reviewDurable objective responsesPrevious anticancer therapyUnacceptable toxic effectsObjective response rateMain adverse reactionsPI3K oncogenic mutations mediate resistance to afatinib in HER2/neu overexpressing gynecological cancers
Bonazzoli E, Cocco E, Lopez S, Bellone S, Zammataro L, Bianchi A, Manzano A, Yadav G, Manara P, Perrone E, Haines K, Espinal M, Dugan K, Menderes G, Altwerger G, Han C, Zeybek B, Litkouhi B, Ratner E, Silasi DA, Huang GS, Azodi M, Schwartz PE, Santin AD. PI3K oncogenic mutations mediate resistance to afatinib in HER2/neu overexpressing gynecological cancers. Gynecologic Oncology 2019, 153: 158-164. PMID: 30630630, PMCID: PMC6430698, DOI: 10.1016/j.ygyno.2019.01.002.Peer-Reviewed Original ResearchMeSH KeywordsAdultAfatinibAgedAnimalsAntineoplastic AgentsCell Line, TumorClass I Phosphatidylinositol 3-KinasesClass Ia Phosphatidylinositol 3-KinaseDrug Resistance, NeoplasmFemaleGenital Neoplasms, FemaleHumansMiceMice, SCIDMiddle AgedMutationPhosphatidylinositol 3-KinasesProtein Kinase InhibitorsReceptor, ErbB-2TransfectionXenograft Model Antitumor AssaysConceptsHER2/neuAKT/mTOR pathwayPIK3CA mutationsMTOR pathwayActivity of afatinibEffect of afatinibPI3K/AKT/mTOR pathwayPotential mechanismsPIK3CA/AKT/mTOR pathwayRapid tumor growthGreater compensatory increasePI3K mutationsAmplification/mutationOncogenic PIK3CA mutationsAfatinib exposurePIK3CA H1047RGynecological cancerClinical trialsMTOR inhibitorsAfatinibTumor growthCompensatory increasePhosphorylated Akt proteinPIK3CA geneC-erb
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 abilityTumorsInhibition of BET Bromodomain Proteins with GS-5829 and GS-626510 in Uterine Serous Carcinoma, a Biologically Aggressive Variant of Endometrial Cancer
Bonazzoli E, Predolini F, Cocco E, Bellone S, Altwerger G, Menderes G, Zammataro L, Bianchi A, Pettinella F, Riccio F, Han C, Yadav G, Lopez S, Manzano A, Manara P, Buza N, Hui P, Wong S, Litkouhi B, Ratner E, Silasi DA, Huang GS, Azodi M, Schwartz PE, Schlessinger J, Santin AD. Inhibition of BET Bromodomain Proteins with GS-5829 and GS-626510 in Uterine Serous Carcinoma, a Biologically Aggressive Variant of Endometrial Cancer. Clinical Cancer Research 2018, 24: 4845-4853. PMID: 29941483, PMCID: PMC6168417, DOI: 10.1158/1078-0432.ccr-18-0864.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAnimalsAntineoplastic AgentsApoptosisAurora Kinase AAurora Kinase BAzepinesCell Line, TumorCell ProliferationCystadenocarcinoma, SerousDose-Response Relationship, DrugEndometrial NeoplasmsExome SequencingFemaleGene Expression Regulation, NeoplasticHumansMiceMiddle AgedPhosphorylationPrimary Cell CultureProteinsProto-Oncogene Proteins c-mycTriazolesUterine NeoplasmsXenograft Model Antitumor AssaysConceptsUterine serous carcinomaPrimary USC cell linesUSC cell linesC-myc expressionCell linesC-MycChemotherapy-resistant diseaseQRT-PCRHigh c-myc expressionDose-dependent decreaseDose-dependent increasePotential therapeutic targetEffective therapeutic agentMouse xenograft modelClin Cancer ResFresh frozen tumor tissueC-myc gene amplificationUSC xenograftsEndometrial cancerAggressive variantSerous carcinomaWhole-exome sequencing studiesClinical studiesConcentrations/dosesXenograft modelImpact of carboplatin hypersensitivity and desensitization on patients with recurrent ovarian cancer
Altwerger G, Florsheim EB, Menderes G, Black J, Schwab C, Gressel GM, Nelson WK, Carusillo N, Passante T, Huang G, Litkouhi B, Azodi M, Silasi DA, Santin A, Schwartz PE, Ratner ES. Impact of carboplatin hypersensitivity and desensitization on patients with recurrent ovarian cancer. Journal Of Cancer Research And Clinical Oncology 2018, 144: 2449-2456. PMID: 30255380, DOI: 10.1007/s00432-018-2753-y.Peer-Reviewed Original ResearchConceptsCarboplatin hypersensitivityCarboplatin desensitizationHypersensitive patientsOverall survivalRisk factorsOvarian cancerTwo-sided Fisher exactAdvanced stage ovarian cancerInfusion of carboplatinRecurrent ovarian cancerIndependent risk factorLonger overall survivalStage ovarian cancerOvarian cancer patientsLong-term treatmentNew risk factorsHigher likelihoodTwo-sided p valueT-testStudent's t-testDesignRetrospective studyGermline BRCA1/2Improved OSLonger OSDesensitization protocol
2017
Objective, domain-specific HER2 measurement in uterine and ovarian serous carcinomas and its clinical significance
Carvajal-Hausdorf DE, Schalper KA, Bai Y, Black J, Santin AD, Rimm DL. Objective, domain-specific HER2 measurement in uterine and ovarian serous carcinomas and its clinical significance. Gynecologic Oncology 2017, 145: 154-158. PMID: 28196634, PMCID: PMC5941302, DOI: 10.1016/j.ygyno.2017.02.002.Peer-Reviewed Original ResearchMeSH KeywordsAdo-Trastuzumab EmtansineAfatinibAntibodies, Monoclonal, HumanizedAntineoplastic AgentsCohort StudiesExtracellular SpaceFemaleFluorescent Antibody TechniqueHumansIntracellular SpaceLapatinibMaytansineMiddle AgedNeoplasms, Cystic, Mucinous, and SerousOvarian NeoplasmsProtein DomainsQuinazolinesReceptor, ErbB-2Retrospective StudiesTissue Array AnalysisTrastuzumabUterine NeoplasmsConceptsUterine serous carcinomaOvarian serous carcinomaHER2 intracellular domainSerous carcinomaECD levelsECD statusTissue microarrayHER2 measurementQuantitative immunofluorescenceHER2 overexpression/amplificationClinico-pathologic characteristicsClinico-pathological featuresHER2-targeted agentsIntracellular domainOverexpression/amplificationHER2 extracellular domainExtracellular domainOSC patientsClinical trialsBreast cancerClinical significancePatientsHER2 assaysP95-HER2CarcinomaDual-Targeting Nanoparticles for In Vivo Delivery of Suicide Genes to Chemotherapy-Resistant Ovarian Cancer Cells
Cocco E, Deng Y, Shapiro EM, Bortolomai I, Lopez S, Lin K, Bellone S, Cui J, Menderes G, Black JD, Schwab CL, Bonazzoli E, Yang F, Predolini F, Zammataro L, Altwerger G, de Haydu C, Clark M, Alvarenga J, Ratner E, Azodi M, Silasi DA, Schwartz PE, Litkouhi B, Saltzman WM, Santin AD. Dual-Targeting Nanoparticles for In Vivo Delivery of Suicide Genes to Chemotherapy-Resistant Ovarian Cancer Cells. Molecular Cancer Therapeutics 2017, 16: 323-333. PMID: 27956521, PMCID: PMC5292071, DOI: 10.1158/1535-7163.mct-16-0501.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsCell Line, TumorCell SurvivalDisease Models, AnimalDrug CarriersDrug Delivery SystemsDrug Resistance, NeoplasmEnterotoxinsFemaleGene ExpressionGene Transfer TechniquesGenes, Transgenic, SuicideGenetic TherapyHumansMiceNanoparticlesOvarian NeoplasmsPromoter Regions, GeneticTumor BurdenXenograft Model Antitumor AssaysConceptsOvarian cancer cellsClostridium perfringens enterotoxinChemotherapy-resistant ovarian cancer cellsIntraperitoneal injectionCancer cellsMultiple intraperitoneal injectionsOvarian cancer xenograftsOvarian tumor cell linesLethal gynecologic cancerTumor-bearing miceOvarian cancer cell deathVivo biodistribution studiesGene therapySuicide gene therapyGynecologic cancerCancer xenograftsOvarian cancerCancer cell deathTherapeutic approachesControl nanoparticlesTumor growthTumor cell linesClaudin-3Biodistribution studiesTumor cells
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 capabilityPrognosisTumorsSYD985, a Novel Duocarmycin-Based HER2-Targeting Antibody–Drug Conjugate, Shows Antitumor Activity in Uterine Serous Carcinoma with HER2/Neu Expression
Black J, Menderes G, Bellone S, Schwab CL, Bonazzoli E, Ferrari F, Predolini F, De Haydu C, Cocco E, Buza N, Hui P, Wong S, Lopez S, Ratner E, Silasi DA, Azodi M, Litkouhi B, Schwartz PE, Goedings P, Beusker PH, van der Lee MM, Timmers CM, Dokter WH, Santin AD. SYD985, a Novel Duocarmycin-Based HER2-Targeting Antibody–Drug Conjugate, Shows Antitumor Activity in Uterine Serous Carcinoma with HER2/Neu Expression. Molecular Cancer Therapeutics 2016, 15: 1900-1909. PMID: 27256376, DOI: 10.1158/1535-7163.mct-16-0163.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAnimalsAntibody-Dependent Cell CytotoxicityAntineoplastic AgentsBystander EffectCathepsin BCell Line, TumorCell SurvivalClass I Phosphatidylinositol 3-KinasesCystadenocarcinoma, SerousDisease Models, AnimalDuocarmycinsFemaleGene ExpressionHumansImmunoconjugatesIndolesMiceMiddle AgedMutationPhosphatidylinositol 3-KinasesPyrrolidinonesReceptor, ErbB-2Survival AnalysisUterine NeoplasmsXenograft Model Antitumor AssaysConceptsUterine serous carcinomaAntibody-dependent cellular cytotoxicityHER2/neu expressionAntibody-drug conjugatesT-DM1Neu expressionHER2-targeting antibody-drug conjugateNovel antibody-drug conjugateNovel HER2-targeting antibody-drug conjugatePrimary USC cell linesHigh HER2 expressionHER2/neu oncogeneHER2/neuMouse xenograft modelUSC cell linesFlow cytometry assayEndometrial cancerSerous carcinomaHER2 expressionTrastuzumab emtansineClinical studiesCellular cytotoxicitySYD985Aggressive formExpress HER2