2025
Preclinical Efficacy of the Estrogen Receptor Degrader Fulvestrant in Combination with RAF/MEK Clamp Avutometinib and FAK Inhibitor in a Low-Grade Serous Ovarian Cancer Animal Model with Acquired Resistance to Chemotherapy and Aromatase Inhibitor
Demirkiran C, Bellone S, Ettorre V, Mansolf M, Hartwich T, McNamara B, Greenman M, Yang-Hartwich Y, Ratner E, Santin N, Sethi N, Palmieri L, Coma S, Pachter J, Ottum S, Santin A. Preclinical Efficacy of the Estrogen Receptor Degrader Fulvestrant in Combination with RAF/MEK Clamp Avutometinib and FAK Inhibitor in a Low-Grade Serous Ovarian Cancer Animal Model with Acquired Resistance to Chemotherapy and Aromatase Inhibitor. International Journal Of Molecular Sciences 2025, 26: 8924. PMID: 41009492, PMCID: PMC12469703, DOI: 10.3390/ijms26188924.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic Combined Chemotherapy ProtocolsAromatase InhibitorsCell Line, TumorDisease Models, AnimalDrug Resistance, NeoplasmFemaleFocal Adhesion Kinase 1FulvestrantHumansMiceMice, SCIDOvarian NeoplasmsProtein Kinase InhibitorsReceptors, EstrogenXenograft Model Antitumor AssaysConceptsPatient-derived tumor xenograftTriple combinationFocal adhesion kinasePreclinical efficacyAromatase inhibitorsClinical evaluationEstrogen receptor (ER)-positiveAcquired resistance to chemotherapyOvarian cancer animal modelEstrogen receptor degrader fulvestrantPatients wild-typeVS-4718Cancer animal modelTumor growth inhibitionLimited treatment optionsResistance to chemotherapyP-ERK levelsFocal adhesion kinase inhibitorMedian survivalRare tumorOvarian carcinomaRecurrence rateTumor xenograftsTreatment optionsFulvestrantPhysician Peer Influence on Salpingectomy Uptake for Tubal Sterilization and Ovarian Cancer Prevention
Xu X, Long J, Pollack C, Desai V, Gross C, Spatz E, Wright J. Physician Peer Influence on Salpingectomy Uptake for Tubal Sterilization and Ovarian Cancer Prevention. JAMA Network Open 2025, 8: e2532998. PMID: 40982280, PMCID: PMC12455378, DOI: 10.1001/jamanetworkopen.2025.32998.Peer-Reviewed Original ResearchConceptsRetrospective cohort studyOpportunistic salpingectomyPeer physiciansInterval sterilizationPostpartum sterilizationTubal sterilizationFallopian tubeClaims dataPhysician patient-sharing networksOvarian cancer riskPatient-sharing networksOvarian cancer preventionInsurance claims dataCesarean deliveryCancer riskProphylactic removalMain OutcomesSalpingectomyCancer preventionCohort studyPeer influenceOperating surgeonPostpartumPhysiciansPatientsEfficacy and Safety of Avutometinib ± Defactinib in Recurrent Low-Grade Serous Ovarian Cancer: Primary Analysis of ENGOT-OV60/GOG-3052/RAMP 201
Banerjee S, Van Nieuwenhuysen E, Aghajanian C, D'Hondt V, Monk B, Clamp A, Prendergast E, Oaknin A, Ring K, Colombo N, Holloway R, Rodrigues M, Chon H, Gourley C, Santin A, Thaker P, Gennigens C, Newman G, Salinas E, Youssoufian H, Moore K, Lustgarten S, O'Malley D, Van Gorp T, Grisham R. Efficacy and Safety of Avutometinib ± Defactinib in Recurrent Low-Grade Serous Ovarian Cancer: Primary Analysis of ENGOT-OV60/GOG-3052/RAMP 201. Journal Of Clinical Oncology 2025, 43: 2782-2792. PMID: 40644648, PMCID: PMC12393057, DOI: 10.1200/jco-25-00112.Peer-Reviewed Original ResearchConceptsLow-grade serous ovarian cancerRecurrent low-grade serous ovarian cancersRandomized phase 3 studySerous ovarian cancerWild-type cohortAdverse eventsMedian durationOvarian cancerSafety profileMedian duration of responseTreatment-related adverse eventsProgression-free survivalDuration of responsePrimary analysisIndependent central reviewOpen-label studyElevated creatine phosphokinaseConfirmed ORRWeeks' monotherapyCombination regimenPlatinum chemotherapyMutation statusCentral reviewMEK inhibitorsPatientsCXCL10-induced regulatory T cells and adenosine signaling promote immunosuppression and progression of epithelial ovarian cancer
Lin A, Moscarelli J, Zhu Y, Lin Z, Ratner E. CXCL10-induced regulatory T cells and adenosine signaling promote immunosuppression and progression of epithelial ovarian cancer. Scientific Reports 2025, 15: 20778. PMID: 40596479, PMCID: PMC12217468, DOI: 10.1038/s41598-025-06812-1.Peer-Reviewed Original ResearchMeSH Keywords5'-NucleotidaseAdenosineAnimalsApyraseB7-H1 AntigenCarcinoma, Ovarian EpithelialCell Line, TumorChemokine CXCL10Disease Models, AnimalDisease ProgressionFemaleHumansImmune ToleranceInterferon-gammaMiceOvarian NeoplasmsReceptors, CXCR3Signal TransductionT-Lymphocytes, RegulatoryTumor MicroenvironmentConceptsEpithelial ovarian cancerImmunosuppressive tumor microenvironmentRegulatory T cellsAdenosine signalingTumor microenvironmentTumor ascitesOvarian cancerT cellsAnti-cancer immune responseEffector T cell activationUp-regulation of Foxp3Epithelial ovarian cancer progressionProgression of epithelial ovarian cancerCell-mediated suppressionSyngeneic mouse modelT cell activationPEO1 cellsPD-L1Inhibitor bevacizumabMouse survivalIL10 productionProlonged survivalPEO4 cellsAMG487 treatmentEOC cellsDatopotamab deruxtecan, a novel TROP2-tareting antibody-drug conjugate with a topoisomerase I inhibitor payload, shows preclinical activity against primary and metastatic uterine and ovarian TROP2 over-expressing carcinosarcoma
Greenman M, Bellone S, Demirkiran C, Hartwich T, Ettorre V, McNamara B, Sethi N, Santin N, Palmieri L, Yang-Hartwich Y, Ratner E, Santin A. Datopotamab deruxtecan, a novel TROP2-tareting antibody-drug conjugate with a topoisomerase I inhibitor payload, shows preclinical activity against primary and metastatic uterine and ovarian TROP2 over-expressing carcinosarcoma. Gynecologic Oncology 2025, 199: 64-71. PMID: 40582040, DOI: 10.1016/j.ygyno.2025.06.017.Peer-Reviewed Original ResearchConceptsCS cell linesPreclinical activityTROP2 expressionPresence of peripheral blood lymphocytesTopoisomerase I inhibitor payloadCell linesRare gynecologic tumorsChromium release assayResistance to chemotherapyTumor growth suppressionPeripheral blood lymphocytesIn vivoAntibody-drug conjugatesOvarian carcinosarcomaRecurrence rateGynecological tumorsNo significant differencePreclinical resultsHealthy donorsBlood lymphocytesPoor prognosisMouse xenograftsChromium releaseClinical trialsCell cytotoxicityPreclinical activity of sacituzumab govitecan in TROP2-positive low-grade serous ovarian cancer patient-derived xenograft models
Ettorre V, Demirkiran C, Bellone S, Niu N, Buza N, Sethi N, Hartwich T, Palmieri L, Santin A. Preclinical activity of sacituzumab govitecan in TROP2-positive low-grade serous ovarian cancer patient-derived xenograft models. International Journal Of Gynecological Cancer 2025, 35: 101988. PMID: 40680453, DOI: 10.1016/j.ijgc.2025.101988.Peer-Reviewed Original ResearchConceptsLow-grade serous ovarian cancerTrophoblast cell surface antigen 2Serous ovarian cancerTrophoblast cell surface antigen 2 expressionSacituzumab govitecanOvarian cancerPatient-derived xenograftsPreclinical activityResistance to chemotherapyPDX modelsAromatase inhibitorsDisease resistant to chemotherapySerous ovarian cancer casesEpithelial ovarian cancer subtypesEffective new treatment optionPatient-derived xenograft modelsSevere combined immunodeficient miceModerate to strong expressionOvarian cancer casesIndolent disease courseOvarian cancer subtypesStandard treatment modalityNew treatment optionsCohort of patientsIn vivoThe role of frozen section in gynecologic pathology
Kaur H, Wang M. The role of frozen section in gynecologic pathology. Seminars In Diagnostic Pathology 2025, 42: 150913. PMID: 40315682, DOI: 10.1016/j.semdp.2025.150913.Peer-Reviewed Original ResearchConceptsTumor sizeHistological typeFrozen sectionsSex cord stromal tumorsCervical stromal involvementExtensive surgical stagingGross tumor sizeOvarian surface involvementUterine mesenchymal tumorsPrimary ovarian tumorsUterine endometrial carcinomaGerm cell tumorsOvarian epithelial tumorsLymph node statusPresence of malignancyLocal tumor invasionSurgery aidsStromal involvementMyometrial involvementSurgical stagingMyometrial invasionOvarian tumorsStromal tumorsNode statusDistant spreadStandard‐Dose Versus High‐Dose Cisplatin for Intermediate/Poor‐Risk Extracranial Malignant Germ Cell Tumors: Re‐Analysis of Pediatric Oncology Group 9049 and Children's Cancer Group 8882 Trial Using Updated MaGIC Risk Stratification
Prior D, Yang J, Nuño M, Shaikh F, Frazier A, Pashankar F. Standard‐Dose Versus High‐Dose Cisplatin for Intermediate/Poor‐Risk Extracranial Malignant Germ Cell Tumors: Re‐Analysis of Pediatric Oncology Group 9049 and Children's Cancer Group 8882 Trial Using Updated MaGIC Risk Stratification. Pediatric Blood & Cancer 2025, 72: e31665. PMID: 40098231, PMCID: PMC12018124, DOI: 10.1002/pbc.31665.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAntineoplastic Combined Chemotherapy ProtocolsBleomycinChildChild, PreschoolCisplatinClinical Trials, Phase II as TopicEtoposideFemaleFollow-Up StudiesHumansMaleMediastinal NeoplasmsMulticenter Studies as TopicNeoplasms, Germ Cell and EmbryonalOvarian NeoplasmsPrognosisRetroperitoneal NeoplasmsRisk AssessmentSecondary Data AnalysisSurvival RateTesticular NeoplasmsConceptsGerm cell tumorsEvent-free survivalOverall survivalStandard of careRisk stratificationCell tumorsExtracranial malignant germ cell tumorsHigh-risk germ cell tumorsMalignant Germ Cell International ConsortiumRetroperitoneal germ cell tumorsOvarian germ cell tumorsMalignant germ cell tumorsHigh-dose cisplatinChildren's Cancer GroupYears of ageStatistically significant differenceMediastinal primaryGCT patientsIntergroup trialPoor riskHDPEBHigh-doseRandomized patientsAdolescent patientsPoor prognosis
2024
Changes in Risk Tolerance for Ovarian Cancer Prevention Strategies during the COVID-19 Pandemic: Results of a Discrete Choice Experiment
Egleston B, Daly M, Lew K, Bealin L, Husband A, Stopfer J, Przybysz P, Tchuvatkina O, Wong Y, Garber J, Rebbeck T. Changes in Risk Tolerance for Ovarian Cancer Prevention Strategies during the COVID-19 Pandemic: Results of a Discrete Choice Experiment. Medical Decision Making 2024, 45: 168-176. PMID: 39722532, PMCID: PMC11881031, DOI: 10.1177/0272989x241302829.Peer-Reviewed Original ResearchConceptsHigher ovarian cancer riskRisk of ovarian cancerRisk-reducing surgeryOvarian cancer riskCancer prevention strategiesCancer riskPrevention strategiesOvarian cancerOvarian cancer prevention strategiesElevated risk of breastRisk of breastCOVID-19 pandemicPrevention scenariosInfluence patients' decisionsRisk-reducing strategiesMedical decision makingAge of menopauseDiscrete choice experimentPatient's decisionElevated riskGenetic testingCOVID-19Menopausal symptomsMedical CenterHeart diseaseOutdoor Air Pollution Exposure and Ovarian Cancer Incidence in a United States–Wide Prospective Cohort Study
Ish J, Chang C, Bookwalter D, Jones R, O’Brien K, Kaufman J, Sandler D, White A. Outdoor Air Pollution Exposure and Ovarian Cancer Incidence in a United States–Wide Prospective Cohort Study. Environmental Health Perspectives 2024, 132: 107701. PMID: 39352804, PMCID: PMC11444316, DOI: 10.1289/ehp14729.Peer-Reviewed Original ResearchOvarian Fibromatosis.
Enea M, Khoshpouri P, Goncalves Filho A, Zaki-Metias K, Rouzrokh P. Ovarian Fibromatosis. RadioGraphics 2024, 44: e240044. PMID: 39052502, DOI: 10.1148/rg.240044.Peer-Reviewed Original ResearchPredictive modeling of gene mutations for the survival outcomes of epithelial ovarian cancer patients
C. M, Lavi E, Altwerger G, Lin Z, Ratner E. Predictive modeling of gene mutations for the survival outcomes of epithelial ovarian cancer patients. PLOS ONE 2024, 19: e0305273. PMID: 38976671, PMCID: PMC11230535, DOI: 10.1371/journal.pone.0305273.Peer-Reviewed Original ResearchConceptsEpithelial ovarian cancerEpithelial ovarian cancer patientsEpithelial ovarian cancer casesGene mutation signaturesPlatinum-based chemotherapyThe Cancer Genome AtlasResponse to treatmentOverall survivalGene mutationsMutational signaturesHomologous recombinationSurvival outcomesIncreased sensitivity to platinum-based chemotherapySensitivity to platinum-based chemotherapyAssociated with increased chemoresistanceResistance to platinum-based chemotherapySurvival timeSurvival rateFavorable response to treatmentPlatinum-induced DNA damageKaplan-Meier survival analysisPrediction of survival outcomesOvarian cancer patientsOverall survival ratePrediction of treatment outcomeMicrotubule-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 settingTherapyEukaryotesCytoskeletonMitosisHeterodimerMotilityTraffickingRegimensReplicationRacial and ethnic differences in epithelial ovarian cancer risk: an analysis from the Ovarian Cancer Association Consortium
Meagher N, White K, Wilkens L, Bandera E, Berchuck A, Carney M, Cramer D, Cushing-Haugen K, Jordan S, Kaufmann S, Le N, Pike M, Riggan M, Qin B, Rothstein J, Titus L, Winham S, Anton-Culver H, Doherty J, Goode E, Pearce C, Risch H, Webb P, Cook L, Goodman M, Harris H, Le Marchand L, McGuire V, Pharoah P, Sarink D, Schildkraut J, Sieh W, Terry K, Thompson P, Whittemore A, Wu A, Peres L, Merritt M. Racial and ethnic differences in epithelial ovarian cancer risk: an analysis from the Ovarian Cancer Association Consortium. American Journal Of Epidemiology 2024, 193: 1242-1252. PMID: 38775277, PMCID: PMC11369223, DOI: 10.1093/aje/kwae076.Peer-Reviewed Original ResearchConceptsOvarian Cancer Association ConsortiumEpithelial ovarian cancer riskNative Hawaiian/Pacific IslanderEpithelial ovarian cancerInverse associationHawaiian/Pacific IslanderRisk associationOdds ratioOvarian cancer riskRisk factor associationsTubal ligationLogistic regression modelsOral contraceptive (OCIslander womenCancer riskFactor associationsWhite participantsPrevention strategiesAsian womenOC useEthnic differencesRisk factorsGynecologic cancerRegression modelsOvarian cancerNiraparib, Dostarlimab, and Bevacizumab as Combination Therapy in Pretreated, Advanced Platinum-Resistant Ovarian Cancer: Findings From Cohort A of the OPAL Phase II Trial
Liu J, Gaillard S, Hendrickson A, Yeku O, Diver E, Jackson C, Arend R, Ratner E, Samnotra V, Gupta D, Chung J, Zhang H, Compton N, Baines A, Bacqué E, Liu X, Felicetti B, Konecny G. Niraparib, Dostarlimab, and Bevacizumab as Combination Therapy in Pretreated, Advanced Platinum-Resistant Ovarian Cancer: Findings From Cohort A of the OPAL Phase II Trial. JCO Precision Oncology 2024, 8: e2300693. PMID: 38754056, PMCID: PMC11371093, DOI: 10.1200/po.23.00693.Peer-Reviewed Original ResearchConceptsPlatinum-resistant ovarian cancerObjective response ratePD-L1 statusAdverse eventsHR deficiencyPD-L1Ovarian cancerCohort AInvestigator-assessed objective response rateTreatment-emergent adverse eventsOn-treatment samplesTreated with niraparibDisease control rateParticipants discontinued treatmentPhase II trialTumor molecular profilingPoor treatment responseBiomarker end pointsPostbaseline scanTriplet therapyRECIST v1.1II trialPrognostic factorsCombination therapyImmune activationTertiary lymphoid structures and B cells determine clinically relevant T cell phenotypes in ovarian cancer
Kasikova L, Rakova J, Hensler M, Lanickova T, Tomankova J, Pasulka J, Drozenova J, Mojzisova K, Fialova A, Vosahlikova S, Laco J, Ryska A, Dundr P, Kocian R, Brtnicky T, Skapa P, Capkova L, Kovar M, Prochazka J, Praznovec I, Koblizek V, Taskova A, Tanaka H, Lischke R, Mendez F, Vachtenheim J, Heinzelmann-Schwarz V, Jacob F, McNeish I, Halaska M, Rob L, Cibula D, Orsulic S, Galluzzi L, Spisek R, Fucikova J. Tertiary lymphoid structures and B cells determine clinically relevant T cell phenotypes in ovarian cancer. Nature Communications 2024, 15: 2528. PMID: 38514660, PMCID: PMC10957872, DOI: 10.1038/s41467-024-46873-w.Peer-Reviewed Original ResearchConceptsHigh-grade serous ovarian carcinomaNon-small cell lung carcinomaTertiary lymphoid structuresCD8+ T cellsT-cell phenotypeTumor mutational burdenT cellsLymphoid structuresB cellsCD8+ T cell compartmentCD8+ T cell phenotypesElevated tumor mutation burdenIntratumoral tertiary lymphoid structuresMature tertiary lymphoid structuresPD1+ T cellsFollicular helper T cellsImmunologically hot tumorB cell profileTumor-infiltrating lymphocytesT cell compartmentAssociated with improved outcomesSerous ovarian carcinomaCell lung carcinomaCohort of patientsHelper T cells
2023
Comparison of the diagnostic efficiency between the O-RADS US risk stratification system and doctors’ subjective judgment
Zhou S, Guo Y, Wen L, Liu J, Fu Y, Xu F, Liu M, Zhao B. Comparison of the diagnostic efficiency between the O-RADS US risk stratification system and doctors’ subjective judgment. BMC Medical Imaging 2023, 23: 190. PMID: 37986051, PMCID: PMC10662783, DOI: 10.1186/s12880-023-01153-9.Peer-Reviewed Original ResearchMeSH KeywordsAdnexal DiseasesFemaleHumansJudgmentOvarian NeoplasmsRetrospective StudiesRisk AssessmentSensitivity and SpecificityUltrasonographyMolecular determinants of clinical outcomes of pembrolizumab in recurrent ovarian cancer: Exploratory analysis of KEYNOTE-100
Ledermann J, Shapira-Frommer R, Santin A, Lisyanskaya A, Pignata S, Vergote I, Raspagliesi F, Sonke G, Birrer M, Provencher D, Sehouli J, Colombo N, González-Martín A, Oaknin A, Ottevanger P, Rudaitis V, Kobie J, Nebozhyn M, Edmondson M, Sun Y, Cristescu R, Jelinic P, Keefe S, Matulonis U. Molecular determinants of clinical outcomes of pembrolizumab in recurrent ovarian cancer: Exploratory analysis of KEYNOTE-100. Gynecologic Oncology 2023, 178: 119-129. PMID: 37862791, DOI: 10.1016/j.ygyno.2023.09.012.Peer-Reviewed Original ResearchNCCN Guidelines® Insights: Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic, Version 2.2024.
Daly M, Pal T, Maxwell K, Churpek J, Kohlmann W, AlHilli Z, Arun B, Buys S, Cheng H, Domchek S, Friedman S, Giri V, Goggins M, Hagemann A, Hendrix A, Hutton M, Karlan B, Kassem N, Khan S, Khoury K, Kurian A, Laronga C, Mak J, Mansour J, McDonnell K, Menendez C, Merajver S, Norquist B, Offit K, Rash D, Reiser G, Senter-Jamieson L, Shannon K, Visvanathan K, Welborn J, Wick M, Wood M, Yurgelun M, Dwyer M, Darlow S. NCCN Guidelines® Insights: Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic, Version 2.2024. Journal Of The National Comprehensive Cancer Network 2023, 21: 1000-1010. PMID: 37856201, DOI: 10.6004/jnccn.2023.0051.Peer-Reviewed Original ResearchMeSH KeywordsBreast NeoplasmsFemaleGenetic Predisposition to DiseaseGenetic TestingGerm-Line MutationHumansMaleOvarian NeoplasmsRisk FactorsConceptsGenetic/Familial High-Risk AssessmentNCCN guidelinesHigh-risk assessmentProstate cancerLP variantsGenetic counseling/testingNCCN Guidelines InsightsRisk of breastLi-Fraumeni syndromeUterine cancerOvarian cancerBreast cancerHereditary predispositionCare strategiesRisk reduction strategiesPathogenic variantsCancerBreastOvarianGender diverse peopleImportant updatesGuidelinesAssessmentSyndromePancreaticLow expression of m6A reader YTHDC1 promotes progression of ovarian cancer via PIK3R1/STAT3/GANAB axis
Wang X, Chen Q, Bing Z, Zhou S, Xu Z, Hou Y, Zhao Y, Zhao S, Wang T. Low expression of m6A reader YTHDC1 promotes progression of ovarian cancer via PIK3R1/STAT3/GANAB axis. International Journal Of Biological Sciences 2023, 19: 4672-4688. PMID: 37781028, PMCID: PMC10535707, DOI: 10.7150/ijbs.81595.Peer-Reviewed Original ResearchConceptsReversible epigenetic modificationAbundant internal modificationPhosphoinositide-3-kinase regulatory subunit 1Glucosidase II alpha subunitRNA immunoprecipitation sequencingM6A reader proteinM6A-dependent mannerRegulatory subunit 1Reader proteinsYTH domainOvarian cancer progressionReader YTHDC1Chromatin immunoprecipitationImmunoprecipitation sequencingWestern blotEpigenetic modificationsGlycan biosynthesisBioinformatics analysisRNA sequencingRNA immunoprecipitationSignal transducerBiological roleGene expressionRegulatory mechanismsTranscription 3
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