grant
Suppression of progesterone receptor signaling by heavy metals promotes tamoxifen resistance and metastasis or ER+ breast cancer
Organization H. LEE MOFFITT CANCER CTR & RES INSTLocation TAMPA, UNITED STATESPosted 24 Jun 2024Deadline 31 Mar 2030
NIHUS FederalResearch GrantFY2025AbscissionActive OxygenAdjuvantAdjuvant TherapyAffectAir PollutionAmino AcidsAnti-Cancer AgentsAntineoplastic AgentsAntineoplastic DrugsAntineoplasticsAntioxidantsAreaArsenicAutomobile DrivingBindingBiologicalBone-Derived Transforming Growth FactorBreast CancerBreast Cancer CellBreast Cancer PatientBreast MetastasisBreast NeoplasmsBreast Tumor PatientBreast TumorsCadmiumCancer DrugCd elementCell NucleusCell ReprogrammingChemoresistanceChromatinClinicalCommunitiesCorpus Luteum HormoneCysteineDataDelta4-pregnene-3,20-dioneDevelopmentDiseaseDisorderDoseDown-RegulationEpigeneticEpigenetic ChangeEpigenetic MechanismEpigenetic ProcessEstrogen ReceptorsExcisionExposure toExtirpationFDA approvedGene Action RegulationGene ExpressionGene Expression RegulationGene RegulationGene Regulation ProcessGene TranscriptionGenesGenetic TranscriptionGoalsH2O2Half-CystineHealthHeavy MetalsHeterochromatinHistonesHydrogen PeroxideHydroperoxideIndividuals from minorityIndividuals of minorityIntermediary MetabolismInternationalInterruptionInterventionL-CysteineL-SerineLeadLinkLow Income PopulationLow incomeLow income groupMalignant Breast NeoplasmMalignant CellMammary CancerMammary NeoplasmsMetabolicMetabolic ProcessesMetabolismMetal exposureMetalsMetastasisMetastasizeMetastatic LesionMetastatic MassMetastatic NeoplasmMetastatic TumorMetastatic breast cancerMetastatic/RecurrentMilk Growth FactorMinorityMinority GroupsMinority PeopleMinority PopulationMinority individualMitochondriaModelingMolecular InteractionNeoplasm MetastasisNeoplastic Disease Chemotherapeutic AgentsNuclearNucleic Acid Regulator RegionsNucleic Acid Regulatory SequencesNucleosomesNucleusOrganellesOrganoidsOxidation-ReductionOxidative StressOxygen RadicalsParticulatePatientsPb elementPhenotypePlatelet Transforming Growth FactorPlayPollutionPregn-4-ene-3,20-dionePregnenedionePrimary NeoplasmPrimary TumorPro-OxidantsProcessProductionProgesteroneProgesterone ReceptorsProgestin ReceptorsPrognosisRNA ExpressionReactive Oxygen SpeciesReceptor SignalingRecommendationRedoxRefractoryRefractory DiseaseRegulationRegulatory RegionsRemovalResistanceRiskRoleSERMsSecondary NeoplasmSecondary TumorSelective Estrogen Receptor ModulatorsSerineSiteStem Cell likeSurgical RemovalTGF BTGF-betaTGF-βTGFbetaTGFβTamoxifenTestingTherapeuticTherapeutic ProgesteroneTranscriptionTransforming Growth Factor betaTransforming Growth Factor-Beta Family GeneTreatment EffectivenessTreatment EfficacyTumor CellTumor-Specific Treatment AgentsVariantVariationWater SupplyWorld Health OrganizationXenograft Modeladjuvant treatmentaminoacidanti-cancer drugarsenicsbiologicbreast cancer metastasisbreast tumor cellcancer cellcancer metastasiscatalasecell transformationcellular reprogrammingchemoresistantchemotherapychemotherapy resistancechemotherapy resistantchromatin remodelingcostcytokinedevelopmentaldisparities in morbiditydrivingenvironmental health disparityepigeneticallyepithelial to mesenchymal transitionexposure to metalfemale treatmentgenetic regulatory elementheavy metal Pbheavy metal leadin vivoindividuals with breast cancerintervention efficacylow income individuallow income peoplemalignant breast tumormammary tumormetastatic breast tumormetastatic mammary cancermetastatic mammary tumormimeticsmitochondrialmitochondrial dysfunctionmorbidity disparitiesmortalitymutantneoplastic cellnoveloxidationoxidation reduction reactionpatients with breast cancerperson with breast cancerpharmacologicpollutantpreventpreventingprogenitor capacityprogenitor cell likeprogenitor-likeprogramsresectionresistantresponse to therapyresponse to treatmentsocial rolesocio-economicsocio-economicallysocioeconomicallysocioeconomicsstem cell characteristicsstem-likestemnesstherapeutic efficacytherapeutic responsetherapy efficacytherapy responsetransformed cellstreat femalestreat womentreatment among femalestreatment among womentreatment in femalestreatment in womentreatment responsetreatment responsivenesstumortumor cell metastasistumor xenograftwomen's treatmentxenograft transplant modelxenotransplant model
Description preview
SUMMARY
The central concept in this project is that exposure of existing estrogen receptor (ER) and
progesterone (PR) positive (ER+/PR+) breast tumors to heavy metal pollutants promotes the
emergence of tumor cells that lack PR expression and function. While ER+/PR+ breast cancer
have excellent prognosis and respond well to treatments, ER+/PR- do…
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