2022
Microtentacle Formation in Ovarian Carcinoma
Reader JC, Fan C, Ory EC, Ju J, Lee R, Vitolo MI, Smith P, Wu S, Ching MMN, Asiedu EB, Jewell CM, Rao GG, Fulton A, Webb TJ, Yang P, Santin AD, Huang HC, Martin SS, Roque DM. Microtentacle Formation in Ovarian Carcinoma. Cancers 2022, 14: 800. PMID: 35159067, PMCID: PMC8834106, DOI: 10.3390/cancers14030800.Peer-Reviewed Original ResearchHuman ovarian surface epitheliumOvarian cancerCell linesCancer cellsMajor therapeutic challengeIntraperitoneal drug deliveryOvarian surface epitheliumOvarian cancer metastasisNew therapeutic targetsDevelopment of chemoresistanceEffect of treatmentBreast cancer cellsOSC cell linesExtrapelvic metastasesMalignant ascitesTherapeutic challengeOvarian carcinomaSurface epitheliumTherapeutic targetMetastatic potentialAscitesCancer metastasisΒ-tubulin isotypesIndividual cancer cellsMetastasis
2020
Derangements in HUWE1/c-MYC pathway confer sensitivity to the BET bromodomain inhibitor GS-626510 in uterine cervical carcinoma
Bonazzoli E, Bellone S, Zammataro L, Gnutti B, Guglielmi A, Pelligra S, Nagarkatti N, Manara P, Tymon-Rosario J, Zeybek B, Altwerger G, Menderes G, Han C, Ratner E, Silasi DA, Huang GS, Andikyan V, Azodi M, Schwartz PE, Santin AD. Derangements in HUWE1/c-MYC pathway confer sensitivity to the BET bromodomain inhibitor GS-626510 in uterine cervical carcinoma. Gynecologic Oncology 2020, 158: 769-775. PMID: 32600791, PMCID: PMC8253557, DOI: 10.1016/j.ygyno.2020.06.484.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAnimalsCell Line, TumorFemaleHumansImidazolesIn Situ Hybridization, FluorescenceIsoxazolesMiceMiddle AgedProteinsProto-Oncogene Proteins c-mycSignal TransductionTumor Suppressor ProteinsUbiquitin-Protein LigasesUterine Cervical NeoplasmsXenograft Model Antitumor AssaysYoung AdultConceptsC-myc expressionC-Myc pathwayTwice-daily oral dosesC-MycWestern blotChemotherapy-resistant diseaseUterine cervical carcinomaPotential therapeutic targetEffective therapeutic agentDose-response decreaseCC xenograftsCell line growthOral dosesCervical carcinomaPrimary tumorDeletion/mutationClinical studiesTherapeutic targetTherapeutic agentsNormal tissuesBET inhibitorsVivo activityQRT-PCRCell proliferationGene deletion/mutation
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 abilityTumors
2017
Moving forward with actionable therapeutic targets and opportunities in endometrial cancer: NCI clinical trials planning meeting report on identifying key genes and molecular pathways for targeted endometrial cancer trials
MacKay HJ, Levine DA, Bae-Jump VL, Bell DW, McAlpine JN, Santin A, Fleming GF, Mutch DG, Nephew KP, Wentzensen N, Goodfellow PJ, Dorigo O, Nijman HW, Broaddus R, Kohn EC. Moving forward with actionable therapeutic targets and opportunities in endometrial cancer: NCI clinical trials planning meeting report on identifying key genes and molecular pathways for targeted endometrial cancer trials. Oncotarget 2017, 5: 84579-84594. PMID: 29137450, PMCID: PMC5663622, DOI: 10.18632/oncotarget.19961.Peer-Reviewed Original ResearchEndometrial cancerClinical trialsEndometrial cancer managementEndometrial cancer trialsFuture clinical trialsActionable therapeutic targetsNCI clinical trialsNational Cancer InstituteHistologic stratificationCancer trialsCancer managementCancer InstituteMortality rateTherapeutic targetTherapeutic directionsNew drugsCancerMolecular pathwaysTrialsMeeting reportSteering CommitteeActionable opportunitiesGroup of expertsKey genesIncidence
2016
Dual CCNE1/PIK3CA targeting is synergistic in CCNE1-amplified/PIK3CA-mutated uterine serous carcinomas in vitro and in vivo
Cocco E, Lopez S, Black J, Bellone S, Bonazzoli E, Predolini F, Ferrari F, Schwab CL, Menderes G, Zammataro L, Buza N, Hui P, Wong S, Zhao S, Bai Y, Rimm DL, Ratner E, Litkouhi B, Silasi DA, Azodi M, Schwartz PE, Santin AD. Dual CCNE1/PIK3CA targeting is synergistic in CCNE1-amplified/PIK3CA-mutated uterine serous carcinomas in vitro and in vivo. British Journal Of Cancer 2016, 115: 303-311. PMID: 27351214, PMCID: PMC4973158, DOI: 10.1038/bjc.2016.198.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsCell Line, TumorClass I Phosphatidylinositol 3-KinasesCyclin EDNA Copy Number VariationsFemaleGene Knockdown TechniquesHeterograftsHumansIn Situ Hybridization, FluorescenceIn Vitro TechniquesMiceMutationOncogene ProteinsPhosphatidylinositol 3-KinasesRNA, MessengerTissue Array AnalysisUterine NeoplasmsConceptsUterine serous carcinomaSerous carcinomaTumor growthCyclin E1 (CCNE1) gene amplificationRecurrent uterine serous carcinomaPrimary USC cell linesNovel therapeutic optionsSingle-agent treatmentIdeal therapeutic targetUSC cell linesCyclin E1 expressionUSC patientsUSC xenograftsInhibited cell growthCell cycle analysisAggressive variantTherapeutic optionsCCNE1 amplificationEndometrial tumorsCYC065Therapeutic targetClinical optionPIK3CA driver mutationsDriver mutationsXenograftsNovel 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
2014
HER2/neu in Endometrial Cancer: A Promising Therapeutic Target With Diagnostic Challenges
Buza N, Roque DM, Santin AD. HER2/neu in Endometrial Cancer: A Promising Therapeutic Target With Diagnostic Challenges. Archives Of Pathology & Laboratory Medicine 2014, 138: 343-50. PMID: 24576030, DOI: 10.5858/arpa.2012-0416-ra.Peer-Reviewed Original ResearchConceptsEndometrial carcinomaHER2/neuPromising therapeutic targetHER2 testingClinical responseTherapeutic targetHumanized monoclonal immunoglobulin G1 antibodyMonoclonal immunoglobulin G1 antibodyUterine serous carcinomaImmunoglobulin G1 antibodyNovel therapeutic strategiesEndometrial cancerSerous adenocarcinomaSerous carcinomaCase reportDiagnostic challengeHER2 overexpressionPathogenetic featuresClinical studiesG1 antibodyTherapeutic strategiesCarcinomaTherapeutic efficacyStandardized criteriaTherapyTargeted 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
2009
Development and characterization of a human single-chain antibody fragment against claudin-3: a novel therapeutic target in ovarian and uterine carcinomas
Romani C, Comper F, Bandiera E, Ravaggi A, Bignotti E, Tassi RA, Pecorelli S, Santin AD. Development and characterization of a human single-chain antibody fragment against claudin-3: a novel therapeutic target in ovarian and uterine carcinomas. American Journal Of Obstetrics And Gynecology 2009, 201: 70.e1-70.e9. PMID: 19426958, PMCID: PMC3701950, DOI: 10.1016/j.ajog.2009.02.010.Peer-Reviewed Original ResearchMeSH KeywordsCarcinoma, PapillaryCell Line, TumorCell SeparationClaudin-3Enzyme-Linked Immunosorbent AssayFemaleFlow CytometryGene LibraryHumansImmunoglobulin FragmentsMembrane ProteinsMicroscopy, ConfocalOvarian NeoplasmsSelf-Sustained Sequence ReplicationSensitivity and SpecificitySurface Plasmon ResonanceUterine Cervical NeoplasmsConceptsClaudin-3Uterine serous carcinoma cell linesSerous papillary carcinomaHuman antibody phage display libraryNovel therapeutic targetEnzyme-linked immunosorbent assayEnzyme-linked immunosorbentHuman single-chain antibody fragmentAntibody phage display libraryCarcinoma cell linesUterine carcinomaNovel antitumor agentsPapillary carcinomaTherapeutic targetSingle-chain antibody fragmentHuman antibodiesHuman malignanciesImmunosorbent assayConformational epitopesPhage display libraryCarcinomaCell linesSurface immunofluorescenceCell surface immunofluorescenceAntitumor agents