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Targeting Oncogenic Drivers in Cancer
Organization DANA-FARBER CANCER INSTLocation BOSTON, UNITED STATESPosted 7 Mar 2022Deadline 28 Feb 2026 ⚠️
NIHUS FederalResearch GrantFY2025AccountingAddressAllelesAllelic ImbalanceAllelomorphsAndrostenedione Aromatase InhibitorAromatase InhibitorsBBB penetrationBeta Cadherin-Associated ProteinBeta-1 CateninBioavailabilityBiologic ModelsBiologicalBiological AvailabilityBiological ModelsBrainBrain MetastasisBrain Nervous SystemBreast CancerBreast NeoplasmsBreast TumorsCTNNBCTNNB1CTNNB1 geneCUL-2Cancer BiologyCancer GenesCancer TreatmentCancer-Promoting GeneCancersCell BodyCell Communication and SignalingCell DeathCell LineCell ReprogrammingCell SignalingCellLineCellsClassificationClinicClinicalClinical OncologyClinical TrialsCoinComplexCytostatic AgentsCytostatic DrugsCytostaticsCytotoxic agentCytotoxic drugDNA mutationDataData SetDevelopmentDiseaseDisease ManagementDisease ResistanceDisorderDisorder ManagementDoxycyclineDrug KineticsDrug TherapyERalphaERαESR1ESR1 geneEarly-Stage Clinical TrialsEncephalonEstradiol Receptor alphaEstradiol Receptor αEstrogen Receptor 1Estrogen Receptor alphaEstrogen Receptor αEstrogen Synthase InhibitorEstrogen Synthetase InhibitorEstrogensEvaluationGene AlterationGene MutationGeneralized GrowthGenerationsGenetic ChangeGenetic defectGenetic mutationGrowthHepatic CancerHepatocarcinomaHepatocellular CarcinomaHepatocellular cancerHepatomaHeterozygoteIncidenceIntermediary MetabolismIntracellular Communication and SignalingInvestigationLicensingLinkLiver Cells CarcinomaLungLung Respiratory SystemMalignant Breast NeoplasmMalignant CellMalignant Neoplasm TherapyMalignant Neoplasm TreatmentMalignant NeoplasmsMalignant TumorMalignant neoplasm of liverMammary CancerMammary NeoplasmsMeasuresMediatingMedicinal ChemistryMetabolic ProcessesMetabolismMetastasisMetastasizeMetastatic LesionMetastatic MassMetastatic NeoplasmMetastatic Neoplasm to the BrainMetastatic TumorMetastatic Tumor to the BrainMetastatic breast cancerMetastatic malignant neoplasm to brainModalityModel SystemModelingMutationNR3A1Neoplasm MetastasisNitrogenNormal CellNormal TissueNormal tissue morphologyOncogenesOncogenicOralPRO2286Pathway interactionsPatientsPenetrancePharmaceutic ChemistryPharmaceutical ChemistryPharmacodynamicsPharmacokineticsPharmacological TreatmentPharmacotherapyPhasePhase 1 Clinical TrialsPhase I Clinical TrialsPhysiologic AvailabilityPositionPositioning AttributePrimary carcinoma of the liver cellsPropertyProteinsProteomicsResistanceSERMsSamplingSecondary NeoplasmSecondary TumorSelective Estrogen Receptor ModulatorsSignal TransductionSignal Transduction SystemsSignalingStrains Cell LinesSystematicsTestingTherapeuticTherapeutic EstrogenTissue GrowthToxic effectToxicitiesTrainingTransforming GenesVibramycinWorkaddictionaddictive disorderalpha-6-Deoxyoxytetracyclineanti-canceranti-cancer therapybeta catbeta cateninbiologicbiological signal transductionblood-brain barrier penetrationbloodbrain barrier penetrationbonebrain micrometastasiscancer cellcancer cell metabolismcancer metabolismcancer metastasiscancer therapycancer typecancer-directed therapycareercellular reprogrammingclinical developmentcomplex datacultured cell linecytotoxicdevelopmentaldriver lesiondriver mutationdrug discoverydrug interventiondrug treatmentexperienceexperimentexperimental researchexperimental studyexperimentsgain of functiongene defectgenome mutationgenomic datagenomic datasetheterozygosityin vivoinsightliver cancerliver carcinomaliver malignancymalignancymalignant breast tumormalignant liver tumormammary tumormetabolism measurementmetabolomicsmetabonomicsmetastatic breast tumormetastatic mammary cancermetastatic mammary tumormortalitymouse modelmurine modelmutantmutant allelenecrocytosisneoplasm/cancerneuron toxicityneuronal toxicityneurotoxicitynovelontogenyoverexpressoverexpressionpathwaypharmaceutical interventionpharmacological interventionpharmacological therapypharmacology interventionpharmacology treatmentpharmacotherapeuticsphase I protocolresistance mechanismresistance to diseaseresistance to therapyresistantresistant diseaseresistant mechanismresistant to diseaseresistant to therapyresponseskillssmall moleculesuccesstargeted drug therapytargeted drug treatmentstargeted therapeutictargeted therapeutic agentstargeted therapytargeted treatmenttherapeutic resistancetherapeutic targettherapy resistanttranslational opportunitiestranslational potentialtreatment resistancetrial planningtumortumor cell metabolismtumor cell metastasistumor eradicationtumor growthtumor metabolismβ-catenin
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Project Summary & Abstract
Targeting estrogen receptor alpha (ERα) is a major anticancer strategy in the treatment of ERα-positive
breast cancer. However, current targeted therapies for ERα have only cytostatic activity and do not induce rapid
quantitative killing of cancer cells, ultimately leading to resistance. A major resistance mechanism is…
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