2024
Pre-clinical efficacy of RAF/MEK clamp avutometinib in combination with FAK inhibition for low-grade serous ovarian cancer
McNamara B, Greenman M, Demirkiran C, Mutlu L, Hartwich T, Bellone S, Manavella D, Zipponi M, Yang-Hartwich Y, Yang K, Ratner E, Schwartz P, Santin A. Pre-clinical efficacy of RAF/MEK clamp avutometinib in combination with FAK inhibition for low-grade serous ovarian cancer. Gynecologic Oncology 2024, 190: s36. DOI: 10.1016/j.ygyno.2024.07.058.Peer-Reviewed Original ResearchPreclinical activity of datopotamab deruxtecan, a novel TROP2 directed antibody-drug conjugate targeting trophoblast cell-surface antigen 2 (TROP2) in ovarian carcinoma
McNamara B, Greenman M, Bellone S, Santin L, Demirkiran C, Mutlu L, Hartwich T, Yang-Hartwich Y, Ratner E, Schwartz P, Santin A. Preclinical activity of datopotamab deruxtecan, a novel TROP2 directed antibody-drug conjugate targeting trophoblast cell-surface antigen 2 (TROP2) in ovarian carcinoma. Gynecologic Oncology 2024, 189: 16-23. PMID: 38981151, DOI: 10.1016/j.ygyno.2024.07.002.Peer-Reviewed Original ResearchTargets trophoblast cell-surface antigen-2Epithelial ovarian cancerAntibody-dependent cellular cytotoxicityPreclinical activityAntibody drug conjugatesOvarian cancerCell linesTumor cellsTrophoblast cell surface antigen 2Cell line-derived xenograft modelFlow cytometryCompared to tumor cellsEpithelial ovarian cancer cell linesOvarian cancer cell linesTumor cells in vitroOvarian cancer patientsPeripheral-blood lymphocytesEOC cell linesTumor growth suppressionAnnexin V-positiveGynecologic cancer mortalityIn vivo antitumor activityCells in vitroPrimary cell linesUnmet medical needTrastuzumab deruxtecan (DS-8201a), a HER2-targeting antibody–drug conjugate, demonstrates in vitro and in vivo antitumor activity against primary and metastatic ovarian tumors overexpressing HER2
Mutlu L, McNamara B, Bellone S, Manavella D, Demirkiran C, Greenman M, Verzosa M, Buza N, Hui P, Hartwich T, Harold J, Yang-Hartwich Y, Zipponi M, Altwerger G, Ratner E, Huang G, Clark M, Andikyan V, Azodi M, Schwartz P, Santin A. Trastuzumab deruxtecan (DS-8201a), a HER2-targeting antibody–drug conjugate, demonstrates in vitro and in vivo antitumor activity against primary and metastatic ovarian tumors overexpressing HER2. Clinical & Experimental Metastasis 2024, 41: 765-775. PMID: 38909139, DOI: 10.1007/s10585-024-10297-z.Peer-Reviewed Original ResearchHigh-grade serous ovarian cancerClear cell carcinomaHER2-targeting antibody-drug conjugateAntibody-drug conjugatesT-DXdReceptor over-expressionTrastuzumab deruxtecanXenograft modelCell linesOvarian clear cell carcinomaOvarian cancer cell linesTumors overexpressing HER2Biologically aggressive tumorsFluorescence in situ hybridization assaySerous ovarian cancerEffective antibody-drug conjugatesIn vivo antitumor activityMouse xenograft modelMetastatic cell linesDS-8201aCancer cell linesAggressive tumorsHER2 expressionCell carcinomaOvarian cancerPreclinical efficacy of RAF/MEK clamp avutometinib in combination with FAK inhibition in low grade serous ovarian cancer
McNamara B, Demirkiran C, Hartwich T, Bellone S, Manavella D, Mutlu L, Greenman M, Zipponi M, Yang-Hartwich Y, Yang K, Ratner E, Schwartz P, Coma S, Pachter J, Santin A. Preclinical efficacy of RAF/MEK clamp avutometinib in combination with FAK inhibition in low grade serous ovarian cancer. Gynecologic Oncology 2024, 183: 133-140. PMID: 38493021, DOI: 10.1016/j.ygyno.2024.01.028.Peer-Reviewed Original ResearchLow grade serous ovarian carcinomaWhole-exome-sequencingGain-of-function mutationsVS-4718Preclinical efficacyLow grade serous ovarian cancerSerous ovarian cancerControl-treated miceTumor growth inhibitionWild-type KRASLoss of heterozygosityDecreased p-ERKRAF/MEK inhibitionMedian survivalOvarian cancerRecurrence rateTherapeutic optionsOral gavageTumor growthTumor samplesIn vivo activityMAPK pathway genesRAF/MEK inhibitorsP-ERKEx vivo
2023
The Poly (ADP-ribose) polymerase inhibitor olaparib and pan-ErbB inhibitor neratinib are highly synergistic in HER2 overexpressing epithelial ovarian carcinoma in vitro and in vivo
Han C, McNamara B, Bellone S, Harold J, Manara P, Hartwich T, Mutlu L, Yang-Hartwich Y, Zipponi M, Demirkiran C, Verzosa M, Altwerger G, Ratner E, Huang G, Clark M, Andikyan V, Azodi M, Dottino P, Schwartz P, Santin A. The Poly (ADP-ribose) polymerase inhibitor olaparib and pan-ErbB inhibitor neratinib are highly synergistic in HER2 overexpressing epithelial ovarian carcinoma in vitro and in vivo. Gynecologic Oncology 2023, 170: 172-178. PMID: 36706643, PMCID: PMC10023457, DOI: 10.1016/j.ygyno.2023.01.015.Peer-Reviewed Original ResearchConceptsCombination of olaparibOvarian cancerHER2 expressionSingle agentCell linesGynecologic cancer mortalityHER2-negative tumorsOvarian cancer cell linesOvarian cancer patientsEpithelial ovarian carcinomaNovel therapeutic optionsOC cell linesUnmet medical needPoly (ADP-ribose) polymerase (PARP) inhibitorsPan-ErbB inhibitorSingle-agent olaparibPolymerase inhibitor olaparibPoly (ADP-ribose) polymerase (PARP) inhibitor olaparibPrimary HER2Cancer cell linesNegative tumorsTherapeutic optionsCancer mortalityCancer patientsNeu expression
2021
A Benzenesulfonamide-based Mitochondrial Uncoupler Induces Endoplasmic Reticulum Stress and Immunogenic Cell Death in Epithelial Ovarian Cancer
Bi F, Jiang Z, Park W, Hartwich TMP, Ge Z, Chong KY, Yang K, Morrison MJ, Kim D, Kim J, Zhang W, Kril LM, Watt DS, Liu C, Yang-Hartwich Y. A Benzenesulfonamide-based Mitochondrial Uncoupler Induces Endoplasmic Reticulum Stress and Immunogenic Cell Death in Epithelial Ovarian Cancer. Molecular Cancer Therapeutics 2021, 20: molcanther.mct-21-0396-a.2021. PMID: 34625503, PMCID: PMC8643344, DOI: 10.1158/1535-7163.mct-21-0396.Peer-Reviewed Original ResearchConceptsEpithelial ovarian cancerImmunogenic cell deathOvarian cancerTumor progressionAntitumor adaptive immune responsesDamage-associated molecular patternsCancer cellsMitochondrial uncouplerAdaptive immune responsesOvarian cancer modelCause of deathCurrent chemotherapeutic agentsNew therapeutic strategiesOvarian cancer cellsCancer cell proliferationCell deathEndoplasmic reticulum stressGynecologic malignanciesClinical outcomesEndoplasmic reticulum stress sensorNew anticancer therapiesPeritoneal fluidInduces Endoplasmic Reticulum StressImmune responseAbdominal cavityEffect of exercise on peritoneal microenvironment and progression of ovarian cancer.
Morrisson M, Bi F, Yang K, Cady S, Hartwich T, Cerchia A, Li Z, Kim J, Irwin M, Yang-Hartwich Y. Effect of exercise on peritoneal microenvironment and progression of ovarian cancer. American Journal Of Cancer Research 2021, 11: 5045-5062. PMID: 34765311, PMCID: PMC8569339.Peer-Reviewed Original ResearchEffects of exerciseOvarian cancerPeritoneal microenvironmentChemotherapy outcomesPatients' health-related qualityBlood urea nitrogen levelsMouse ovarian cancer modelIncidence of neutropeniaIntraperitoneal fat tissueProduction of CCL2Role of CCL2Health-related qualityDeadliest gynecological malignancyMetastatic ovarian cancerExercise-induced changesUrea nitrogen levelsOvarian cancer modelOvarian carcinoma progressionPotential beneficial effectsCancer cell viabilityPeritoneal colonizationCo-culture modelChronic exerciseClinical outcomesGynecological malignanciesPersonalized models of heterogeneous 3D epithelial tumor microenvironments: Ovarian cancer as a model
Horst EN, Bregenzer ME, Mehta P, Snyder CS, Repetto T, Yang-Hartwich Y, Mehta G. Personalized models of heterogeneous 3D epithelial tumor microenvironments: Ovarian cancer as a model. Acta Biomaterialia 2021, 132: 401-420. PMID: 33940195, PMCID: PMC8969826, DOI: 10.1016/j.actbio.2021.04.041.Peer-Reviewed Original ResearchConceptsOptimal adjuvant treatmentTumor microenvironmentOvarian cancerCancer modelAdverse clinical outcomesHeterogeneous patient populationMinimal residual diseaseDifferent tumor locationsConventional cancer treatmentsEpithelial tumor microenvironmentModels of cancerAdjuvant treatmentDurable responsesTreatment failureClinical outcomesResidual diseasePatient populationTumor locationDisease progressionEffective therapyFundamental cancer biologyDiverse tumor microenvironmentsIndividual patientsSame patientPatient biopsies
2020
In vivo modeling of metastatic human high-grade serous ovarian cancer in mice
Kim O, Park EY, Klinkebiel DL, Pack SD, Shin YH, Abdullaev Z, Emerson RE, Coffey DM, Kwon SY, Creighton CJ, Kwon S, Chang EC, Chiang T, Yatsenko AN, Chien J, Cheon DJ, Yang-Hartwich Y, Nakshatri H, Nephew KP, Behringer RR, Fernández FM, Cho CH, Vanderhyden B, Drapkin R, Bast RC, Miller KD, Karpf AR, Kim J. In vivo modeling of metastatic human high-grade serous ovarian cancer in mice. PLOS Genetics 2020, 16: e1008808. PMID: 32497036, PMCID: PMC7297383, DOI: 10.1371/journal.pgen.1008808.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsCell Line, TumorChromosomal InstabilityCystadenocarcinoma, SerousDEAD-box RNA HelicasesDisease Models, AnimalDNA RepairDrug Resistance, NeoplasmDrug Screening Assays, AntitumorFeasibility StudiesFemaleHumansMiceMice, KnockoutMutationNeoplasm GradingNeoplasm MetastasisOvarian NeoplasmsPeritoneal NeoplasmsPrimary Cell CulturePTEN PhosphohydrolaseRibonuclease IIITumor Suppressor Protein p53ConceptsHigh-grade serous carcinomaHuman HGSCHigh-grade serous ovarian cancerSerous ovarian cancerOvarian cancerPeritoneal metastasisHuman high-grade serous ovarian cancerMetastatic ovarian cancerOvarian cancer typesHuman cancer metastasisHuman cancer mortalityHemorrhagic ascitesClinical metastasisHistopathological similaritiesSerous carcinomaCancer mortalityFallopian tubeMurine modelPeritoneal cavityMouse modelPotential therapyMouse deathMetastasisCancer typesCancer metastasis
2019
Tumor microenvironment and immunology of ovarian cancer: 12th Biennial Rivkin Center Ovarian Cancer Research Symposium
Mitra AK, Yang-Hartwich Y. Tumor microenvironment and immunology of ovarian cancer: 12th Biennial Rivkin Center Ovarian Cancer Research Symposium. International Journal Of Gynecological Cancer 2019, 29: s12. PMID: 31462543, DOI: 10.1136/ijgc-2019-000666.Peer-Reviewed Original Research
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
2016
TRX-E-002-1 Induces c-Jun–Dependent Apoptosis in Ovarian Cancer Stem Cells and Prevents Recurrence In Vivo
Alvero AB, Heaton A, Lima E, Pitruzzello M, Sumi N, Yang-Hartwich Y, Cardenas C, Steinmacher S, Silasi DA, Brown D, Mor G. TRX-E-002-1 Induces c-Jun–Dependent Apoptosis in Ovarian Cancer Stem Cells and Prevents Recurrence In Vivo. Molecular Cancer Therapeutics 2016, 15: 1279-1290. PMID: 27196760, DOI: 10.1158/1535-7163.mct-16-0005.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisCell Line, TumorCell ProliferationCell SurvivalCisplatinDrug Resistance, NeoplasmDrug SynergismFemaleFlavonoidsGene Expression Regulation, NeoplasticHumansMiceNeoplasm Recurrence, LocalNeoplasm TransplantationNeoplastic Stem CellsOvarian NeoplasmsPhosphorylationProto-Oncogene Proteins c-junSignal TransductionXenograft Model Antitumor AssaysConceptsCancer stem cellsOvarian cancer cellsTumor burdenOvarian cancerCancer cellsChemoresistant cancer stem cellsOvarian cancer stem cellsIntraperitoneal tumor burdenRecurrent ovarian cancerBest therapeutic optionManagement of patientsCombination of cisplatinEpithelial ovarian cancerCell deathStem cellsTumor repairDisease recurrenceMaintenance treatmentPatient survivalTherapeutic optionsHigh mortalityStemness propertiesMonotherapyDeathVehicle control
2014
Murine Model for Non-invasive Imaging to Detect and Monitor Ovarian Cancer Recurrence
Sumi NJ, Lima E, Pizzonia J, Orton SP, Craveiro V, Joo W, Holmberg JC, Gurrea M, Yang-Hartwich Y, Alvero A, Mor G. Murine Model for Non-invasive Imaging to Detect and Monitor Ovarian Cancer Recurrence. Journal Of Visualized Experiments 2014, 51815. PMID: 25407815, PMCID: PMC4353409, DOI: 10.3791/51815.Peer-Reviewed Original ResearchConceptsRecurrent ovarian cancerOvarian cancerVisible light rangeAnatomical locationOptical imaging platformAvailable chemotherapy agentsLethal gynecologic malignancyOvarian cancer recurrenceEpithelial ovarian cancerNovel therapy optionsAppropriate animal modelsMultiple angular positionsLight rangeIdentification of tumorsGynecologic malignanciesRecurrent diseaseSurgical debulkingChemoresistant diseaseCombination chemotherapyClinical profileNon-invasive imagingTherapy optionsCancer recurrenceX-rayChemotherapy agentsOvulation and extra-ovarian origin of ovarian cancer
Yang-Hartwich Y, Gurrea-Soteras M, Sumi N, Joo WD, Holmberg JC, Craveiro V, Alvero AB, Mor G. Ovulation and extra-ovarian origin of ovarian cancer. Scientific Reports 2014, 4: 6116. PMID: 25135607, PMCID: PMC4137344, DOI: 10.1038/srep06116.Peer-Reviewed Original ResearchConceptsOvarian cancerExtra-ovarian originMalignant cellsChemokines/cytokinesOvarian surface epitheliumBetter prevention strategiesPotential molecular mechanismsFallopian tubeLate diagnosisOvarian localizationGastrointestinal tractSDF-1Mortality ratePrevention strategiesSurface epitheliumMain chemoattractantVivo modelLethal diseaseEx vivoCancerEarly detectionSpecific markersOvulationOvariesTumors
2013
Phenotypic modifications in ovarian cancer stem cells following Paclitaxel treatment
Craveiro V, Yang-Hartwich Y, Holmberg JC, Joo WD, Sumi NJ, Pizzonia J, Griffin B, Gill SK, Silasi DA, Azodi M, Rutherford T, Alvero AB, Mor G. Phenotypic modifications in ovarian cancer stem cells following Paclitaxel treatment. Cancer Medicine 2013, 2: 751-762. PMID: 24403249, PMCID: PMC3892380, DOI: 10.1002/cam4.115.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic Agents, PhytogenicCarcinoma, Ovarian EpithelialDrug Resistance, NeoplasmFemaleHEK293 CellsHumansHyaluronan ReceptorsMiceMice, NudeMyeloid Differentiation Factor 88Neoplasms, Glandular and EpithelialNeoplastic Stem CellsOvarian NeoplasmsPaclitaxelPhenotypeRecurrenceSnail Family Transcription FactorsTranscription FactorsTumor BurdenXenograft Model Antitumor AssaysConceptsEpithelial ovarian cancerRecurrent epithelial ovarian cancerOvarian cancer stem cellsEOC stem cellsCancer stem cellsQuantitative polymerase chain reactionRecurrent diseaseOvarian cancerEOC cellsVivo ovarian cancer modelsStem cellsDoses of paclitaxelLethal gynecologic malignancyOvarian cancer modelProcess of recurrenceWestern blot analysisMaintenance therapyGynecologic malignanciesPrimary diseaseAggressive diseaseEOC patientsPrimary tumorPolymerase chain reactionAggressive phenotypePaclitaxel treatmentTLR2 enhances ovarian cancer stem cell self-renewal and promotes tumor repair and recurrence
Chefetz I, Alvero A, Holmberg J, Lebowitz N, Craveiro V, Yang-Hartwich Y, Yin G, Squillace L, Soteras M, Aldo P, Mor G. TLR2 enhances ovarian cancer stem cell self-renewal and promotes tumor repair and recurrence. Cell Cycle 2013, 12: 511-521. PMID: 23324344, PMCID: PMC3587452, DOI: 10.4161/cc.23406.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarcinoma, Ovarian EpithelialDrug Resistance, NeoplasmFemaleHomeodomain ProteinsHumansHyaluronan ReceptorsInflammationMiceMice, NudeMyeloid Differentiation Factor 88Nanog Homeobox ProteinNeoplasm Recurrence, LocalNeoplasms, Glandular and EpithelialNeoplastic Stem CellsNF-kappa BOctamer Transcription Factor-3Ovarian NeoplasmsSOXB1 Transcription FactorsToll-Like Receptor 2Tumor Cells, CulturedTumor MicroenvironmentConceptsOvarian cancer stem cellsCancer stem cellsTumor repairEOC stem cellsTLR2-MyD88NFκB pathwaySpecific pro-inflammatory pathwaysStem cellsMajority of patientsEpithelial ovarian cancer stem cellsPrimary ovarian cancerPro-inflammatory pathwaysPro-inflammatory microenvironmentCell populationsStemness-associated genesChemoresistant recurrent diseaseRecurrent diseaseEOC patientsRecent compelling evidenceOvarian cancerTumor injuryRecurrenceCancer cell populationsTumor initiationCancer cells
2011
Prevalence of Epithelial Ovarian Cancer Stem Cells Correlates with Recurrence in Early‐Stage Ovarian Cancer
Steffensen KD, Alvero AB, Yang Y, Waldstrøm M, Hui P, Holmberg JC, Silasi DA, Jakobsen A, Rutherford T, Mor G. Prevalence of Epithelial Ovarian Cancer Stem Cells Correlates with Recurrence in Early‐Stage Ovarian Cancer. Journal Of Oncology 2011, 2011: 620523. PMID: 21904548, PMCID: PMC3166719, DOI: 10.1155/2011/620523.Peer-Reviewed Original ResearchEarly-stage ovarian cancerCancer stem cellsEOC stem cellsOvarian cancer stem cellsProgression-free survivalEpithelial ovarian cancer stem cellsNumber of CD44Ovarian cancerShorter progression-free survivalStem cellsOvarian cancer tumorsPredictors of diseaseTreatment selectionCancer tumorsCancerCD44RecurrenceTumorsSurvivalCellsHigher numberPatientsCK18PrevalenceChemoresistanceOvarian cancer stem cells and inflammation
Mor G, Yin G, Chefetz I, Yang Y, Alvero A. Ovarian cancer stem cells and inflammation. Cancer Biology & Therapy 2011, 11: 708-713. PMID: 21317559, PMCID: PMC3100563, DOI: 10.4161/cbt.11.8.14967.Peer-Reviewed Original ResearchConceptsEpithelial ovarian cancerOvarian cancerCancer stem cellsAdvanced stage ovarian cancerOvarian cancer stem cellsGynecologic cancer deathFourth leading causeCancer-related deathSource of recurrenceLack of responseStem cellsCancer deathDisease progressionLeading causeQuestion of recurrenceRecurrenceCancerChemotherapyDeathInflammationChemoresistanceCauseCellsProgressionWomen