2022
Intersections of endocrine pathways and the epithelial mesenchymal transition in endometrial cancer
Gelissen JH, Huang GS. Intersections of endocrine pathways and the epithelial mesenchymal transition in endometrial cancer. Frontiers In Oncology 2022, 12: 914405. PMID: 36052252, PMCID: PMC9424890, DOI: 10.3389/fonc.2022.914405.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsEpithelial-mesenchymal transitionEndometrial cancerMesenchymal transitionRegulation of EMTTherapeutic interventionsInvasive capacityCancer metastasisEpithelial originEndocrine pathwaysMesenchymal phenotypeCancerCancer cellsEndocrine signalingMetastasisSignaling pathwaysCritical regulatorMortalityPathwayPotential avenuesSynergistic 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
A phase 2 evaluation of pembrolizumab for recurrent Lynch‐like versus sporadic endometrial cancers with microsatellite instability
Bellone S, Roque DM, Siegel ER, Buza N, Hui P, Bonazzoli E, Guglielmi A, Zammataro L, Nagarkatti N, Zaidi S, Lee J, Silasi D, Huang GS, Andikyan V, Damast S, Clark M, Azodi M, Schwartz PE, Tymon‐Rosario J, Harold JA, Mauricio D, Zeybek B, Menderes G, Altwerger G, Ratner E, Alexandrov LB, Iwasaki A, Kong Y, Song E, Dong W, Elvin JA, Choi J, Santin AD. A phase 2 evaluation of pembrolizumab for recurrent Lynch‐like versus sporadic endometrial cancers with microsatellite instability. Cancer 2021, 128: 1206-1218. PMID: 34875107, PMCID: PMC9465822, DOI: 10.1002/cncr.34025.Peer-Reviewed Original ResearchConceptsObjective response rateImmune checkpoint inhibitorsProgression-free survivalEndometrial cancerWhole-exome sequencingSporadic endometrial cancerOverall survivalEnd pointPhase 2 pilot studyPrimary end pointSecondary end pointsTumor mutation burdenPhase 2 evaluationLarger confirmatory studiesAntigen processing/presentationProcessing/presentationCheckpoint inhibitorsSurgical resectionICI resistanceDMMR patientsPrognostic significanceDMMR tumorsMechanisms of resistanceLocal treatmentSporadic MSIPrognostic impact of mismatch repair deficiency in high- and low-intermediate-risk, early-stage endometrial cancer following vaginal brachytherapy
Li JY, Park HS, Huang GS, Young MR, Ratner E, Santin A, Damast S. Prognostic impact of mismatch repair deficiency in high- and low-intermediate-risk, early-stage endometrial cancer following vaginal brachytherapy. Gynecologic Oncology 2021, 163: 557-562. PMID: 34602287, DOI: 10.1016/j.ygyno.2021.09.018.Peer-Reviewed Original ResearchConceptsRecurrence-free survivalEndometrioid endometrial cancerVaginal brachytherapyPMMR patientsOverall survivalEEC patientsEndometrial cancerExact testThree-year recurrence-free survivalEarly-stage endometrial cancerCox proportional hazards regressionPoor recurrence-free survivalAdjuvant vaginal brachytherapyThree-year OSMultivariable Cox regressionLympho-vascular invasionSignificant prognostic variablesProportional hazards regressionLog-rank testKaplan-Meier estimatesDeficient mismatch repairMismatch repair statusFisher's exact testMismatch repair deficiencyDMMR statusDHES0815A, 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 variantsSex Hormones, Insulin, and Insulin-like Growth Factors in Recurrence of High-Stage Endometrial CancerSex Hormones and Insulin in Endometrial Cancer Recurrence
Merritt MA, Strickler HD, Hutson AD, Einstein MH, Rohan TE, Xue X, Sherman ME, Brinton LA, Yu H, Miller DS, Ramirez NC, Lankes HA, Birrer MJ, Huang GS, Gunter MJ. Sex Hormones, Insulin, and Insulin-like Growth Factors in Recurrence of High-Stage Endometrial CancerSex Hormones and Insulin in Endometrial Cancer Recurrence. Cancer Epidemiology Biomarkers & Prevention 2021, 30: 719-726. PMID: 33622671, PMCID: PMC8026669, DOI: 10.1158/1055-9965.epi-20-1613.Peer-Reviewed Original ResearchConceptsEndometrial cancer recurrenceSex hormonesEndometrial cancerProgesterone receptorCancer recurrenceInsulin/insulin-like growth factor axisRecurrence riskInsulin-like growth factor (IGF) axisInsulin-like growth factorGynecologic Oncology GroupProgression-free survivalEndometrial adenocarcinoma patientsIGF-binding proteinsFuture clinical trialsGrowth factor axisConfidence intervalsIR/IGF1RAdjuvant therapyER positivityIGFBP-3Oncology GroupProspective cohortAdenocarcinoma patientsPretreatment specimensSerum concentrations
2020
Population-Based Screening for Endometrial Cancer: Human vs. Machine Intelligence
Hart GR, Yan V, Huang GS, Liang Y, Nartowt BJ, Muhammad W, Deng J. Population-Based Screening for Endometrial Cancer: Human vs. Machine Intelligence. Frontiers In Artificial Intelligence 2020, 3: 539879. PMID: 33733200, PMCID: PMC7861326, DOI: 10.3389/frai.2020.539879.Peer-Reviewed Original ResearchAverage-risk womenEndometrial cancerRisk womenOvarian Cancer Screening TrialEndometrial cancer riskCancer Screening TrialPrimary care physiciansPopulation-based screeningCancer risk predictionHealth dataCare physiciansGynecologic oncologistsRisk stratificationDisease onsetPositive rateIndividual patientsCancer riskInvasive proceduresScreening TrialPersonal health dataEarly cancer detectionMortality rateEarly screeningFalse positive ratePrevious risk modelsSacituzumab 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
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-38
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 modelIn 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
Genetic landscape of clear cell endometrial cancer and the era of precision medicine
Huang GS, Santin AD. Genetic landscape of clear cell endometrial cancer and the era of precision medicine. Cancer 2017, 123: 3216-3218. PMID: 28485840, PMCID: PMC5907932, DOI: 10.1002/cncr.30743.Commentaries, Editorials and Letters
2015
PTEN expression in benign human endometrial tissue and cancer in relation to endometrial cancer risk factors
Yang HP, Meeker A, Guido R, Gunter MJ, Huang GS, Luhn P, d’Ambrosio L, Wentzensen N, Sherman ME. PTEN expression in benign human endometrial tissue and cancer in relation to endometrial cancer risk factors. Cancer Causes & Control 2015, 26: 1729-1736. PMID: 26376893, PMCID: PMC4628559, DOI: 10.1007/s10552-015-0666-5.Peer-Reviewed Original ResearchConceptsEndometrial cancer risk factorsCancer risk factorsEndometrial cancer tissuesEndometrial tissueRisk factorsBenign endometriumNSAID usePTEN lossEndometrial cancerEndometrial glandsPTEN expressionExact testCancer tissuesPopulation-based case-control studyBenign endometrial samplesBenign endometrial tissuesMost risk factorsHuman endometrial tissueCase-control studyFisher's exact testEndometrial hyperplasiaEndometrial carcinomaEndometrial samplesEutopic endometriumImmunohistochemical study