grant
Investigation of ecDNA as a driver of intratumoral heterogeneity and treatment resistance in high-risk medulloblastoma
Organization SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTELocation LA JOLLA, UNITED STATESPosted 1 Sept 2023Deadline 31 Aug 2028
NIHUS FederalResearch GrantFY20250-11 years oldBET bromodomain inhibitorBET inhibitorBETiBiologicalBiopsyBromodomain and Extra-Terminal motif inhibitorBromodomains and extra-terminal domain inhibitorCRISPRCRISPR/Cas systemCancer GenesCancer PatientCancer-Promoting GeneCancersCell BodyCellsChemotherapy and RadiationChemotherapy and/or radiationChildChild YouthChildhood Malignant Brain TumorChildren (0-21)Children's HospitalCircular DNAClinicalClustered Regularly Interspaced Short Palindromic RepeatsCodeCoding SystemCombined Modality TherapyComputing MethodologiesDNADNA Damage RepairDNA RepairDNA dependent protein kinase catalytic subunitDNA-PKcsDataData BanksDatabanksDeoxyribonucleic AcidDependenceDevelopmentDiseaseDisease ProgressionDisorderEnhancersFunctional RNAFunctional dependenceGene AmplificationGene TranscriptionGenesGenetic TranscriptionHumanImageIn VitroIndividualInstitutionIntratumoral heterogeneityInvestigationMYCNMYCN geneMalignant NeoplasmsMalignant TumorMediatingMedulloblastomaMetastasisMetastasizeMetastatic LesionMetastatic MassMetastatic NeoplasmMetastatic TumorMethodsMissionModern ManMolecularMolecular AnalysisMolecular EvolutionMonitorMultimodal TherapyMultimodal TreatmentNHEJNMYCNMYC GeneNational Institutes of HealthNeoplasm MetastasisNervous System InjuriesNervous System TraumaNervous System damageNeurological DamageNeurological InjuryNeurological traumaNon-Homologous End JoiningNon-homologous DNA End JoiningNoncoding RNANonhomologous DNA End JoiningNonhomologous End JoiningNontranslated RNAOncogene ProductsOncogene ProteinsOncogenesOncoproteinsOutcomePARP InhibitorPARP-1 inhibitorPARPiPDX modelPathogenesisPatient derived xenograftPatientsPediatric HospitalsPediatric Malignant Brain TumorPoly(ADP-ribose) Polymerase InhibitorPoly(ADP-ribose) polymerase 1 inhibitorPredispositionPreventionPrimary NeoplasmPrimary TumorProcessProliferatingPropertyPublic HealthRNA ExpressionRelapseResearchResistanceRoleSamplingSecondary NeoplasmSecondary TumorSingle-Nucleus SequencingSubgroupSusceptibilityTestingTherapeuticTranscriptionTransforming GenesTreatment EfficacyTreatment FailureTumor BiologyTumor CellTumorigenicityUnited States National Institutes of HealthUnscheduled DNA SynthesisUntranslated RNAVariantVariationWorkbiologicbromodomain extra-terminal inhibitorcancer genomicscancer metastasischemo/radiation therapychemotherapy and radiotherapychildhood brain cancercohortcombination therapycombinatorialcombined modality treatmentcombined treatmentcomputational methodologycomputational methodscomputer based methodcomputer methodscomputing methoddata depositorydata repositorydata set repositorydataset repositorydetection methoddetection proceduredetection techniquedevelopmentaldevelopmental diseasedevelopmental disorderentire genomeexperimentexperimental researchexperimental studyexperimentsextrachromosomal DNAfull genomegenome sequencingheterogeneity in tumorshigh riskhuman diseaseimagingimprovedin vivoinhibitorinnovateinnovationinnovativeintervention efficacyintra-tumoral heterogeneityintratumor heterogeneitykidsmalignancymulti-modal therapymulti-modal treatmentmultiomicsmultiple omicsnatural gene amplificationneoplasm/cancerneoplastic cellneurotraumanew therapeutic approachnew therapeutic interventionnew therapeutic strategiesnew therapy approachesnew treatment approachnew treatment strategynoncodingnovelnovel therapeutic approachnovel therapeutic interventionnovel therapeutic strategiesnovel therapy approachoncogenomicspanomicspatient derived xenograft modelpediatric brain cancerpre-clinical studypreclinical studyradiation or chemotherapyreconstructionresistance to therapyresistantresistant to therapysNuc-Seqsingle nucleus RNA-sequencingsingle nucleus seqsingle-nucleus RNA-seqsnRNA sequencingsnRNA-seqsocial rolestandard carestandard of carestandard treatmenttargeted drug therapytargeted drug treatmentstargeted therapeutictargeted therapeutic agentstargeted therapytargeted treatmenttherapeutic efficacytherapeutic resistancetherapeutic targettherapy efficacytherapy failuretherapy resistanttreatment resistancetumortumor cell metastasistumor growthtumor heterogeneitywhole genomeyoungster
Description preview
The overall objective of this proposal is to investigate circular extrachromosomal DNA (ecDNA) as a potential
driver of intratumoral heterogeneity and treatment resistance in medulloblastoma, the most common pediatric
malignant brain tumor. Intratumoral heterogeneity is one of the leading determinants of therapeutic resistance
and treatment…
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