grant
Molecular Determinants of Response and Resistance to EZH2 and PARP inhibition in Prostate Cancer
Organization DANA-FARBER CANCER INSTLocation BOSTON, UNITED STATESPosted 1 Sept 2023Deadline 31 Aug 2028
NIHUS FederalResearch GrantFY2025AcuteAdenocarcinomaAndrogen ReceptorAutomobile DrivingBiologicalBiological MarkersBiopsyCastrationCell BodyCell Communication and SignalingCell SignalingCellsChromatinClassificationClinicalClinical DataClinical ResearchClinical StudyClinical TrialsCombined Modality TherapyComplexDF/HCCDNA DamageDNA Damage RepairDNA InjuryDNA MethylationDNA RepairDNA Repair GeneDNA Repair PathwayDNA repair proteinDana-Farber Cancer InstituteDataDependenceDevelopmentDiseaseDisorderEnhancersEpigeneticEpigenetic ChangeEpigenetic MechanismEpigenetic ProcessEpithelioid Cell SarcomaEpithelioid SarcomasExpression SignatureFDA approvedGene Down-RegulationGene Expression ProfileGeneHomologGenomicsHeterogeneityHistone H3HomologHomologous GeneHomologueIntracellular Communication and SignalingInvestigatorsL-LysineLysineMalignant AdenomaMalignant neoplasm of prostateMalignant prostatic tumorMeasuresMediatingMedicalMesotheliomaMethylationModelingMolecularMultimodal TherapyMultimodal TreatmentNHEJNeuroendocrineNeuroendocrine Prostate CancerNeuroendocrine SystemNeurosecretory SystemsNon-Hodgkin's LymphomaNon-Homologous End JoiningNon-homologous DNA End JoiningNonhodgkins LymphomaNonhomologous DNA End JoiningNonhomologous End JoiningPARP InhibitorPARP inhibitionPARP-1 inhibitorPARPiPDX modelPatient derived xenograftPatientsPhase 1/2 Clinical TrialPhase I/II Clinical TrialPhenotypePhosphorylationPlayPoly(ADP-ribose) Polymerase InhibitorPoly(ADP-ribose) polymerase 1 inhibitorPolycombProcessProstateProstate AdenocarcinomaProstate CAProstate CA therapyProstate CancerProstate Cancer therapyProstate GlandProstate Gland AdenocarcinomaProstate malignancyProstatic GlandProtein PhosphorylationReceptor SignalingRegulationRepressionRepressor ProteinsResearch PersonnelResearchersResistanceRoleRouteSignal TransductionSignal Transduction SystemsSignalingSurgical CastrationSynoviomaSystematicsTherapy Clinical TrialsTranscription RepressionTranscription RepressorTranscriptional RepressorTumor CellUnscheduled DNA Synthesisadvanced diseaseadvanced illnessadvanced prostate cancerandrogen independent prostate cancerandrogen indifferent prostate cancerandrogen insensitive prostate cancerandrogen resistance in prostate cancerandrogen resistant prostate cancerbio-markersbiologicbiologic markerbiological signal transductionbiomarkerbiomarker identificationcastration resistant CaPcastration resistant PCacastration resistant prostate cancercofactorcombination therapycombined modality treatmentcombined treatmentderepressiondevelopmentaldrivingdrug sensitivityepigeneticallyepigenomicsgene expression patterngene expression signaturegene repairgene repressiongenetic repressorhistone methylationhomologous recombinationhomologous recombination deficiencyhomologous recombination repair deficiencyhormone refractory prostate canceridentification of biomarkersidentification of new biomarkersinhibitorinhibitor druginhibitor therapeuticinhibitor therapyinsightmarker identificationmembermenmulti-modal therapymulti-modal treatmentneoplastic cellneuroendocrine phenotypenew therapeutic approachnew therapeutic interventionnew therapeutic strategiesnew therapy approachesnew treatment approachnew treatment strategynon-Hodgkins diseasenovelnovel therapeutic approachnovel therapeutic interventionnovel therapeutic strategiesnovel therapy approachoverexpressoverexpressionpatient derived xenograft modelpatient subclasspatient subclusterpatient subgroupspatient subpopulationspatient subsetspatient subtypespharmacodynamic biomarkerpharmacodynamic markerpre-clinical studypreclinical studyprogramsprostate cancer modelprostate cancer progressionprostate cancer resistant to androgenprostate cancer treatmentprostate tumor modelprostatic adenocarcinomarepressor complexresistance to therapyresistantresistant to therapyresponseresponse biomarkerresponse markerssafety assessmentsocial rolesynergismsynovial cell sarcomasynovial sarcomasynthetic lethal interactionsynthetic lethalitytargeted drug therapytargeted drug treatmentstargeted therapeutictargeted therapeutic agentstargeted therapytargeted treatmenttherapeutic resistancetherapy durationtherapy resistanttranscriptional profiletranscriptional signaturetreatment resistancetumortumor growth
Description preview
PROJECT SUMMARY- PROJECT 2
Castration resistant prostate cancer (CRPC) is a lethal disease. Epigenetic dysregulation, including
overexpression of the enhancer of zeste homolog 2 (EZH2) drives treatment resistance, and EZH2 inhibitors are
in clinical trials. Beyond its canonical role as a member of the PRC2 complex as a transcriptional repressor,…
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