2022
Synergistic activity of neratinib in combination with olaparib in uterine serous carcinoma overexpressing HER2/neu
Yadav G, Roque DM, Bellone S, Manavella DD, Hartwich TMP, Zipponi M, Harold J, Tymon-Rosario J, Mutlu L, Altwerger G, Menderes G, Ratner E, Buza N, Hui P, Huang GS, Andikyan V, Clark M, Azodi M, Schwartz PE, Alexandrov LB, Santin AD. Synergistic activity of neratinib in combination with olaparib in uterine serous carcinoma overexpressing HER2/neu. Gynecologic Oncology 2022, 166: 351-357. PMID: 35641325, DOI: 10.1016/j.ygyno.2022.05.021.Peer-Reviewed Original ResearchConceptsUterine serous carcinomaHER2/neu expressionHER2/neuCombination of olaparibUSC xenograftsUSC cell linesNeu expressionSerous carcinomaLow HER2/neu expressionHER2/neu 3Cell linesHER2/neu gene amplificationNovel therapeutic optionsPolymerase inhibitor olaparibNeu gene amplificationDurable growth inhibitionNeratinib treatmentUSC cellsUSC patientsEndometrial cancerAggressive variantTherapeutic optionsPoor prognosisHER2/Single agent
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 variantsTrastuzumab tolerability in the treatment of advanced (stage III-IV) or recurrent uterine serous carcinomas that overexpress HER2/neu
Tymon-Rosario J, Siegel ER, Bellone S, Harold J, Adjei N, Zeybek B, Mauricio D, Altwerger G, Menderes G, Ratner E, Clark M, Andikyan V, Huang GS, Azodi M, Schwartz PE, Fader AN, Santin AD. Trastuzumab tolerability in the treatment of advanced (stage III-IV) or recurrent uterine serous carcinomas that overexpress HER2/neu. Gynecologic Oncology 2021, 163: 93-99. PMID: 34372971, PMCID: PMC8721852, DOI: 10.1016/j.ygyno.2021.07.033.Peer-Reviewed Original ResearchMeSH KeywordsAgedCystadenocarcinoma, SerousFemaleHumansMiddle AgedNeoplasm Recurrence, LocalNeoplasm StagingReceptor, ErbB-2TrastuzumabUterine NeoplasmsConceptsUterine serous carcinomaRecurrent uterine serous carcinomaAdverse eventsTreatment armsSerous carcinomaExperimental armToxicity profileTreatment-related adverse eventsTrastuzumab maintenance therapyCarboplatin/paclitaxelCardiac adverse eventsEndometrial cancer patientsGastrointestinal adverse eventsManageable toxicity profilePhase II trialEfficacy of trastuzumabSystem organ classII trialMaintenance therapyPrimary endpointSecondary endpointsMaintenance treatmentSafety profileCancer patientsCumulative toxicity
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-38Precision Therapy for Aggressive Endometrial Cancer by Reactivation of Protein Phosphatase 2A
Haines K, Huang GS. Precision Therapy for Aggressive Endometrial Cancer by Reactivation of Protein Phosphatase 2A. Cancer Research 2019, 79: 4009-4010. PMID: 31416848, DOI: 10.1158/0008-5472.can-19-1938.Commentaries, Editorials and Letters
2018
Inhibition 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 modelA novel multiple biomarker panel for the early detection of high-grade serous ovarian carcinoma
Han C, Bellone S, Siegel ER, Altwerger G, Menderes G, Bonazzoli E, Egawa-Takata T, Pettinella F, Bianchi A, Riccio F, Zammataro L, Yadav G, Marto JA, Penet MF, Levine DA, Drapkin R, Patel A, Litkouhi B, Ratner E, Silasi DA, Huang GS, Azodi M, Schwartz PE, Santin AD. A novel multiple biomarker panel for the early detection of high-grade serous ovarian carcinoma. Gynecologic Oncology 2018, 149: 585-591. PMID: 29572027, PMCID: PMC5986604, DOI: 10.1016/j.ygyno.2018.03.050.Peer-Reviewed Original ResearchMeSH KeywordsBiomarkers, TumorCase-Control StudiesCystadenocarcinoma, SerousFemaleGene ExpressionHumansMesothelinMiddle AgedNeoplasm GradingOvarian NeoplasmsROC CurveConceptsHigh-grade serous ovarian carcinomaSerous ovarian carcinomaIL-6Ovarian cancerOvarian carcinomaE-cadHigh-grade serous ovarian adenocarcinomaEarly-stage ovarian cancerROC analysisEarly detectionMajority of patientsLethal gynecologic malignancyStage ovarian cancerOvarian cancer patientsBenign gynecologic pathologyNon-cancer controlsSerous ovarian adenocarcinomaEffective cancer screeningSerous ovarian cancerMultiple biomarker panelsFour-marker panelHigh differential gene expressionGynecologic malignanciesCA 125IL-1ra
2014
Insulin-Like Growth Factor 2 Silencing Restores Taxol Sensitivity in Drug Resistant Ovarian Cancer
Brouwer-Visser J, Lee J, McCullagh K, Cossio MJ, Wang Y, Huang GS. Insulin-Like Growth Factor 2 Silencing Restores Taxol Sensitivity in Drug Resistant Ovarian Cancer. PLOS ONE 2014, 9: e100165. PMID: 24932685, PMCID: PMC4059749, DOI: 10.1371/journal.pone.0100165.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic Agents, PhytogenicApoptosisBlotting, WesternCell CycleCell ProliferationCystadenocarcinoma, SerousDrug Resistance, NeoplasmFemaleHumansInsulin-Like Growth Factor IInsulin-Like Growth Factor IIMiceMice, NudeOvarian NeoplasmsPaclitaxelPhosphorylationReal-Time Polymerase Chain ReactionReceptor, IGF Type 1Reverse Transcriptase Polymerase Chain ReactionRNA, MessengerRNA, Small InterferingSignal TransductionTumor Cells, CulturedXenograft Model Antitumor AssaysConceptsDrug-resistant ovarian cancerResistant ovarian cancerInsulin-like growth factorIGF2 knockdownOvarian cancerPotential therapeutic targetDrug resistanceTherapeutic targetCell linesOvarian cancer xenograft modelDrug-sensitive cell linesOvarian cancer cohortTaxol sensitivityOvarian cancer cell linesCancer xenograft modelExtreme drug resistanceDose of TaxolDrug-resistant cellsCancer Genome Atlas (TCGA) dataNovel potential targetSensitive cell linesCancer cell linesShort hairpin RNAClinical indicatorsCancer cohort
2011
Phase II trial of adjuvant pelvic radiation “sandwiched” between combination paclitaxel and carboplatin in women with uterine papillary serous carcinoma
Einstein MH, Frimer M, Kuo D, Reimers LL, Mehta K, Mutyala S, Huang GS, Hou JY, Goldberg GL. Phase II trial of adjuvant pelvic radiation “sandwiched” between combination paclitaxel and carboplatin in women with uterine papillary serous carcinoma. Gynecologic Oncology 2011, 124: 21-25. PMID: 22035806, PMCID: PMC3681611, DOI: 10.1016/j.ygyno.2011.10.007.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsBrachytherapyCarboplatinCarcinoma, PapillaryCystadenocarcinoma, SerousDose Fractionation, RadiationDrug Administration ScheduleFemaleHumansMiddle AgedNeoplasm StagingPaclitaxelRadiotherapy, AdjuvantUterine NeoplasmsConceptsAdjuvant pelvic radiationCycles of paclitaxelCycles of chemotherapyRadiation therapyPelvic radiationCarboplatin chemotherapyUterine papillary serous carcinomaExtra-uterine diseaseModality adjuvant therapyNon-hematologic toxicitiesPrescribed radiation therapyVisible residual diseasePhase II trialKaplan-Meier methodPapillary serous carcinomaStage 3Stage 1Combination paclitaxelOverall PFSAdjuvant therapyChemotherapy cyclesII trialMedian ageResidual diseaseSerous carcinomaPerformance of Serum CA125 as a Prognostic Biomarker in Patients With Uterine Papillary Serous Carcinoma
Gupta D, Gunter MJ, Yang K, Lee S, Zuckerwise L, Chen LM, Goldberg GL, Huang GS. Performance of Serum CA125 as a Prognostic Biomarker in Patients With Uterine Papillary Serous Carcinoma. International Journal Of Gynecological Cancer 2011, 21: 529-534. PMID: 21436701, DOI: 10.1097/igc.0b013e31821091b5.Peer-Reviewed Original ResearchConceptsUterine papillary serous carcinomaPapillary serous carcinomaCA125 levelsLymph node metastasisDisease recurrenceCA125 elevationMetastatic diseaseNode metastasisSerum CA125Serous carcinomaStage III/IV diseaseCox proportional hazards regression modelingProportional hazards regression modelingElevated CA125 levelsPreoperative CA125 levelsLymph node involvementRecurrence-free survivalAdvanced International FederationMultivariate survival analysisUPSC patientsMean followSurgical stagingCA125 measurementNode involvementIndependent predictors