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
2022
Safety and activity of anti-mesothelin antibody–drug conjugate anetumab ravtansine in combination with pegylated-liposomal doxorubicin in platinum-resistant ovarian cancer: multicenter, phase Ib dose escalation and expansion study
Santin A, Vergote I, González-Martín A, Moore K, Oaknin A, Romero I, Diab S, Copeland L, Monk B, Coleman R, Herzog T, Siegel J, Kasten L, Schlicker A, Schulz A, Köchert K, Walter A, Childs B, Elbi C, Bulat I. Safety and activity of anti-mesothelin antibody–drug conjugate anetumab ravtansine in combination with pegylated-liposomal doxorubicin in platinum-resistant ovarian cancer: multicenter, phase Ib dose escalation and expansion study. International Journal Of Gynecological Cancer 2022, 33: ijgc-2022-003927. PMID: 36564099, PMCID: PMC10086500, DOI: 10.1136/ijgc-2022-003927.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Ovarian EpithelialDoxorubicinDrug Resistance, NeoplasmFemaleHumansImmunoconjugatesOvarian NeoplasmsPolyethylene GlycolsConceptsPlatinum-resistant ovarian cancerProgression-free survivalMedian progression-free survivalAnetumab ravtansineObjective response rateOvarian cancerLiposomal doxorubicinMedian durationAdverse eventsDose escalationMesothelin expressionCommon treatment-emergent adverse eventsPlatinum-resistant epithelial ovarian cancerResponse rateAnti-mesothelin monoclonal antibodyTreatment-emergent adverse eventsHigh mesothelin expressionPegylated-liposomal doxorubicinPhase Ib studyPhase III studyDose-limiting toxicityPromising clinical activityEpithelial ovarian cancerAnti-tumor activityCentral immunohistochemistry
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
2019
PARP-1 activity (PAR) determines the sensitivity of cervical cancer to olaparib
Bianchi A, Lopez S, Altwerger G, Bellone S, Bonazzoli E, Zammataro L, Manzano A, Manara P, Perrone E, Zeybek B, Han C, Menderes G, Ratner E, Silasi DA, Huang GS, Azodi M, Newberg JY, Pavlick DC, Elvin J, Frampton GM, Schwartz PE, Santin AD. PARP-1 activity (PAR) determines the sensitivity of cervical cancer to olaparib. Gynecologic Oncology 2019, 155: 144-150. PMID: 31434613, PMCID: PMC6788971, DOI: 10.1016/j.ygyno.2019.08.010.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsApoptosisCell Growth ProcessesCell Line, TumorDose-Response Relationship, DrugDrug Resistance, NeoplasmFemaleG2 Phase Cell Cycle CheckpointsHumansM Phase Cell Cycle CheckpointsMice, SCIDMiddle AgedPhthalazinesPiperazinesPoly (ADP-Ribose) Polymerase-1Poly(ADP-ribose) Polymerase InhibitorsUterine Cervical NeoplasmsXenograft Model Antitumor AssaysYoung AdultConceptsPoly (ADP-ribose) polymerase (PARP) inhibitorsCervical cancerCC cell linesCell linesPARP-1 activityOverall animal survivalMajor health problemCC cell growthXenograft tumor growthWestern blot assaysG2/M phaseVivo antitumor activityCC xenograftsCC patientsPreclinical activityPAR expressionCell cycle arrestOvarian cancerPrimary cell linesOlaparib treatmentUseful biomarkerHealth problemsTumor growthAnimal survivalOlaparib activityPrevalence 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 characterizationBiopsyClinicTumorsPI3K 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
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 optionsIn vitro and in vivo activity of IMGN853, an Antibody-Drug Conjugate targeting Folate Receptor Alpha linked to DM4, in biologically aggressive endometrial cancers
Altwerger G, Bonazzoli E, Bellone S, Egawa-Takata T, Menderes G, Pettinella F, Bianchi A, Riccio F, Feinberg J, Zammataro L, Han C, Yadav G, Dugan K, Morneault A, Ponte JF, Buza N, Hui P, Wong S, Litkouhi B, Ratner E, Silasi DA, Huang GS, Azodi M, Schwartz PE, Santin AD. In vitro and in vivo activity of IMGN853, an Antibody-Drug Conjugate targeting Folate Receptor Alpha linked to DM4, in biologically aggressive endometrial cancers. Molecular Cancer Therapeutics 2018, 17: molcanther.0930.2017. PMID: 29440294, PMCID: PMC5932245, DOI: 10.1158/1535-7163.mct-17-0930.Peer-Reviewed Original ResearchConceptsEndometrial cancerXenograft modelCell linesTumor cell linesPatient-derived xenograft modelsUterine cancer cell linesAggressive endometrial cancersEndometrial cancer deathsExpression of FRαPrimary USC cell linesRecurrent endometrial cancerReceptor alpha expressionUSC cell linesImpressive antitumor activityMol Cancer TherUSC patientsCancer cell linesMedian survivalCancer deathPDX modelsPreclinical dataUterine cancerComplete resolutionIMGN853Grade 3
2017
FOXM1 expression is significantly associated with chemotherapy resistance and adverse prognosis in non-serous epithelial ovarian cancer patients
Tassi RA, Todeschini P, Siegel ER, Calza S, Cappella P, Ardighieri L, Cadei M, Bugatti M, Romani C, Bandiera E, Zanotti L, Tassone L, Guarino D, Santonocito C, Capoluongo ED, Beltrame L, Erba E, Marchini S, D’Incalci M, Donzelli C, Santin AD, Pecorelli S, Sartori E, Bignotti E, Odicino F, Ravaggi A. FOXM1 expression is significantly associated with chemotherapy resistance and adverse prognosis in non-serous epithelial ovarian cancer patients. Journal Of Experimental & Clinical Cancer Research 2017, 36: 63. PMID: 28482906, PMCID: PMC5422964, DOI: 10.1186/s13046-017-0536-y.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorCarcinoma, Ovarian EpithelialCell Line, TumorCell MovementCell ProliferationCell Transformation, NeoplasticCystadenocarcinoma, SerousDisease ProgressionDNA RepairDrug Resistance, NeoplasmFemaleForkhead Box Protein M1Gene Expression ProfilingGene Expression Regulation, NeoplasticGene Knockdown TechniquesHumansKaplan-Meier EstimateMiddle AgedNeoplasm GradingNeoplasm MetastasisNeoplasm StagingNeoplasms, Glandular and EpithelialOvarian NeoplasmsPrognosisProtein IsoformsRNA, Small InterferingConceptsForkhead box M1FOXM1 expressionEOC cell linesSerous EOCNormal controlsEOC subtypesCox proportional hazards analysisWorse disease-specific survivalEpithelial ovarian cancer patientsCell linesPlatinum-resistant casesSnap-frozen biopsiesDisease-specific survivalPlatinum-resistant diseaseAdvanced FIGO stageProportional hazards analysisProtein overexpressionClinic-pathological parametersOvarian cancer patientsRT-qPCRTransient siRNA transfectionPARP inhibitor olaparibFIGO stageSerous histologySpecific survivalDual-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
Polymerase 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 capabilityPrognosisTumorsMolecular diagnosis and molecular profiling to detect treatment-resistant ovarian cancer
English DP, Menderes G, Black J, Schwab CL, Santin AD. Molecular diagnosis and molecular profiling to detect treatment-resistant ovarian cancer. Expert Review Of Molecular Diagnostics 2016, 16: 769-782. PMID: 27169329, DOI: 10.1080/14737159.2016.1188692.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic AgentsBiomarkers, TumorDrug Resistance, NeoplasmFemaleHumansMolecular Diagnostic TechniquesOrganoplatinum CompoundsOvarian NeoplasmsPaclitaxelConceptsChemo-resistant diseaseOvarian cancerMolecular profilingOptimal cytoreductive surgeryRecurrent ovarian cancerEpithelial ovarian cancerLong non-coding RNA expressionLong-term survivalAbsence of improvementCancer stem cellsStem cell markersAdjuvant chemotherapyCytoreductive surgeryNon-coding RNA expressionCancer 5Gynecologic tumorsMEDLINE searchNew agentsMolecular mediatorsTerm survivalCancerCell markersDiseaseRNA expressionChromosomal aberrations
2015
Solitomab, an EpCAM/CD3 bispecific antibody construct (BiTE®), is highly active against primary uterine and ovarian carcinosarcoma cell lines in vitro
Ferrari F, Bellone S, Black J, Schwab CL, Lopez S, Cocco E, Bonazzoli E, Predolini F, Menderes G, Litkouhi B, Ratner E, Silasi DA, Azodi M, Schwartz PE, Santin AD. Solitomab, an EpCAM/CD3 bispecific antibody construct (BiTE®), is highly active against primary uterine and ovarian carcinosarcoma cell lines in vitro. Journal Of Experimental & Clinical Cancer Research 2015, 34: 123. PMID: 26474755, PMCID: PMC4609066, DOI: 10.1186/s13046-015-0241-7.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntibodies, BispecificAntigens, NeoplasmAntineoplastic AgentsCarcinosarcomaCD3 ComplexCell Adhesion MoleculesCell Line, TumorCell ProliferationCoculture TechniquesCytokinesCytotoxicity, ImmunologicDrug Resistance, NeoplasmEpithelial Cell Adhesion MoleculeFemaleFlow CytometryHumansKiller Cells, NaturalLymphocyte ActivationMiddle AgedOvarian NeoplasmsT-Lymphocytes, CytotoxicUterine NeoplasmsConceptsCS cell linesPeripheral blood lymphocytesT cellsEpCAM/CD3-bispecific antibodyCell linesT cell-mediated killingT-cell activation markersFlow cytometryCD3 bispecific antibodyChromium release assaysT cell proliferationCarcinosarcoma cell lineFlow cytometry assaySingle-chain antibody constructCS cellsPositive cell linesH 51CrOvarian carcinosarcomaPleural effusionActivation markersGynecologic tumorsPoor prognosisCS patientsRecurrent/Blood lymphocytes
2014
Solitomab, an epithelial cell adhesion molecule/CD3 bispecific antibody (BiTE), is highly active against primary chemotherapy‐resistant ovarian cancer cell lines in vitro and fresh tumor cells ex vivo
English DP, Bellone S, Schwab CL, Roque DM, Lopez S, Bortolomai I, Cocco E, Bonazzoli E, Chatterjee S, Ratner E, Silasi D, Azodi M, Schwartz PE, Rutherford TJ, Santin AD. Solitomab, an epithelial cell adhesion molecule/CD3 bispecific antibody (BiTE), is highly active against primary chemotherapy‐resistant ovarian cancer cell lines in vitro and fresh tumor cells ex vivo. Cancer 2014, 121: 403-412. PMID: 25251053, PMCID: PMC4304922, DOI: 10.1002/cncr.29062.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, BispecificAntigens, NeoplasmCarcinoma, Ovarian EpithelialCD3 ComplexCell Adhesion MoleculesCell Line, TumorCytotoxicity, ImmunologicDrug Resistance, NeoplasmEpithelial Cell Adhesion MoleculeFemaleFlow CytometryHumansMiddle AgedNeoplasms, Glandular and EpithelialOvarian NeoplasmsT-LymphocytesConceptsOvarian cancer cell linesPeripheral blood lymphocytesTumor cellsCancer cell linesFlow cytometryBlood lymphocytesCell linesMalignant cellsChemotherapy-resistant cell linesChemotherapy-resistant ovarian cancerT cell-mediated killingT-cell activation markersCell-mediated cytotoxicity assayEpCAM expressionPrimary ovarian cancer cell linesFresh ovarian tumorsChemotherapy-resistant diseaseCD3 bispecific antibodyTumor-associated lymphocytesEpithelial ovarian carcinoma cell linesT cell cytotoxicityChromium release assaysFresh tumor cellsOvarian tumor cell linesOvarian tumor cellsTargeted 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 β-tubulin overexpression within the tumor microenvironment is a prognostic biomarker for poor overall survival in ovarian cancer patients treated with neoadjuvant carboplatin/paclitaxel
Roque DM, Buza N, Glasgow M, Bellone S, Bortolomai I, Gasparrini S, Cocco E, Ratner E, Silasi DA, Azodi M, Rutherford TJ, Schwartz PE, Santin AD. Class III β-tubulin overexpression within the tumor microenvironment is a prognostic biomarker for poor overall survival in ovarian cancer patients treated with neoadjuvant carboplatin/paclitaxel. Clinical & Experimental Metastasis 2013, 31: 101-110. PMID: 24005572, PMCID: PMC3947146, DOI: 10.1007/s10585-013-9614-5.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorCarboplatinCystadenocarcinoma, SerousDrug Resistance, NeoplasmFemaleHumansImmunohistochemistryNeoadjuvant TherapyOvarian NeoplasmsPaclitaxelPrognosisReal-Time Polymerase Chain ReactionTubulinTumor MicroenvironmentUp-RegulationConceptsClass III β-tubulinIII β-tubulinClass III β-tubulin expressionNeoadjuvant chemotherapyPoor overall survivalOverall survivalΒ-tubulin expressionClass III β-tubulin overexpressionPrimary cytoreductionNeoadjuvant carboplatin/paclitaxelPoor median overall survivalTumor microenvironmentAdvanced ovarian carcinomaCarboplatin/paclitaxelMedian overall survivalOvarian cancer patientsCell linesCancer stem cellsNeoadjuvant carboplatinPrimary debulkingVitro chemosensitivityClinical outcomesPatient populationCancer patientsStromal expressionOncogenic PIK3CA gene mutations and HER2/neu gene amplifications determine the sensitivity of uterine serous carcinoma cell lines to GDC-0980, a selective inhibitor of Class I PI3 kinase and mTOR kinase (TORC1/2)
English DP, Bellone S, Cocco E, Bortolomai I, Pecorelli S, Lopez S, Silasi DA, Schwartz PE, Rutherford T, Santin AD. Oncogenic PIK3CA gene mutations and HER2/neu gene amplifications determine the sensitivity of uterine serous carcinoma cell lines to GDC-0980, a selective inhibitor of Class I PI3 kinase and mTOR kinase (TORC1/2). American Journal Of Obstetrics And Gynecology 2013, 209: 465.e1-465.e9. PMID: 23891627, DOI: 10.1016/j.ajog.2013.07.020.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic AgentsBridged Bicyclo Compounds, HeterocyclicCarcinoma, PapillaryCell Line, TumorClass I Phosphatidylinositol 3-KinasesDrug Resistance, NeoplasmEndometrial NeoplasmsFemaleGene AmplificationGenes, erbB-2HumansIn Situ Hybridization, FluorescenceMiddle AgedMutationPhosphatidylinositol 3-KinasesPyrimidinesTOR Serine-Threonine KinasesConceptsClass I PI3-kinasePI3-kinaseC-erbB2 gene amplificationOncogenic PIK3CA mutationsMTOR kinaseCell linesGene amplificationUterine serous carcinoma cell linesDownstream cellular responsesCarcinoma cell linesUSC cell linesGene mutationsCellular responsesKinaseDifferential growth inhibitionDNA sequencingDirect DNA sequencingMutationsSitu hybridizationUse of GDCGrowth inhibitionExon 9HER2/neu gene amplificationFishPrimary USC cell linesTubulin‐β‐III overexpression by uterine serous carcinomas is a marker for poor overall survival after platinum/taxane chemotherapy and sensitivity to epothilones
Roque DM, Bellone S, English DP, Buza N, Cocco E, Gasparrini S, Bortolomai I, Ratner E, Silasi D, Azodi M, Rutherford TJ, Schwartz PE, Santin AD. Tubulin‐β‐III overexpression by uterine serous carcinomas is a marker for poor overall survival after platinum/taxane chemotherapy and sensitivity to epothilones. Cancer 2013, 119: 2582-2592. PMID: 23585021, PMCID: PMC3700638, DOI: 10.1002/cncr.28017.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorCystadenocarcinoma, SerousDrug Resistance, NeoplasmEpothilonesFemaleGene Expression Regulation, NeoplasticHumansKaplan-Meier EstimateMiddle AgedNeoplasm StagingPaclitaxelPlatinum CompoundsPredictive Value of TestsPrognosisReal-Time Polymerase Chain ReactionTubulinTubulin ModulatorsUp-RegulationUterine NeoplasmsConceptsUterine serous carcinomaOvarian serous carcinomaOverall survivalSerous carcinomaP-glycoproteinClinical outcomesPaclitaxel resistanceTreatment of USCPlatinum/taxane chemotherapyPoor overall survivalFresh frozen tissue samplesReal-time polymerase chain reactionCell linesTaxane chemotherapyEndometrial cancerPoor outcomePoor prognosisPolymerase chain reactionFresh frozen tissueMedian inhibitory concentrationClinical investigationSubset of individualsGlycoprotein expressionCarcinomaImmunohistochemistryClass III β-tubulin overexpression in ovarian clear cell and serous carcinoma as a maker for poor overall survival after platinum/taxane chemotherapy and sensitivity to patupilone
Roque DM, Bellone S, Buza N, Romani C, Cocco E, Bignotti E, Ravaggi A, Rutherford TJ, Schwartz PE, Pecorelli S, Santin AD. Class III β-tubulin overexpression in ovarian clear cell and serous carcinoma as a maker for poor overall survival after platinum/taxane chemotherapy and sensitivity to patupilone. American Journal Of Obstetrics And Gynecology 2013, 209: 62.e1-62.e9. PMID: 23583215, DOI: 10.1016/j.ajog.2013.04.017.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic AgentsATP Binding Cassette Transporter, Subfamily B, Member 1Cell LineCystadenocarcinoma, SerousDose-Response Relationship, DrugDown-RegulationDrug Resistance, NeoplasmEpothilonesFemaleHumansImmunohistochemistryKaplan-Meier EstimateMicrotubulesNeoplasms, Glandular and EpithelialOvarian NeoplasmsPaclitaxelPrognosisReal-Time Polymerase Chain ReactionTaxoidsTubulinTubulin ModulatorsConceptsClass III β-tubulinClear cell carcinomaIII β-tubulinCell carcinomaOverall survivalP-glycoproteinClass III β-tubulin overexpressionClinical outcomesPolymerase chain reactionPaclitaxel resistanceClass III β-tubulin expressionPlatinum/taxane chemotherapyPoor overall survivalSerous papillary carcinomaChain reactionOvarian clear cellFresh frozen tissue samplesReal-time polymerase chain reactionCell linesTime polymerase chain reactionPolymerase chain reaction resultsΒ-tubulin expressionTaxane chemotherapyPoor outcomePoor prognosis