grant
Elucidating resistance mechanisms and enhancing response to immune checkpoint blockade in central nervous system metastases from breast cancer
Organization MASSACHUSETTS GENERAL HOSPITALLocation BOSTON, UNITED STATESPosted 12 Jul 2024Deadline 30 Jun 2029
NIHUS FederalResearch GrantFY2025After CareAfter-TreatmentAftercareAnatomic SitesAnatomic structuresAnatomyAntigen PresentationAutomobile DrivingBloodBlood Reticuloendothelial SystemBody TissuesBrainBrain MetastasisBrain Nervous SystemBreast CancerBreast Cancer PatientBreast MetastasisBreast NeoplasmsBreast Tumor PatientBreast TumorsCDK Inhibitor ProteinCDK4CDK4 geneCDK4ICDKI ProteinCDKN2CDKN2 GenesCDKN2ACDKN2A geneCMM2CNS MetastasisCNS Nervous SystemCancersCarcinomatosisCell BodyCell Division Kinase 4CellsCentral Nervous SystemCentral Nervous System MetastasisCephalicCerebrospinal FluidCheckpoint inhibitorClinicalClinical DataClinical TrialsClonal EvolutionClonal ExpansionCombined Modality TherapyCommon NeoplasmCommon TumorComplicationComputational toolkitCranialCyclin Kinase InhibitorCyclin-Dependent Kinase 4Cyclin-Dependent Kinase InhibitorCyclin-Dependent Kinase Inhibitor 2A GeneCyclin-Dependent KinasesCyclin-Dependent Protein KinasesDNA AlterationDNA FingerprintingDNA ProfilingDNA Sequence AlterationDNA TypingDataDevelopmentDiseaseDisorderEncephalonExclusionFailureFlow CytofluorometriesFlow CytofluorometryFlow CytometryFlow MicrofluorimetryFlow MicrofluorometryFutureGene TranscriptionGeneticGenetic AlterationGenetic DeterminismGenetic DifferentiationGenetic DivergenceGenetic DriftGenetic FingerprintingsGenetic TranscriptionGoalsGrantIFNINK4INK4AImmuneImmune checkpoint inhibitorImmune mediated therapyImmune systemImmunesImmunochemical ImmunologicImmunologicImmunologicalImmunologicallyImmunologically Directed TherapyImmunologicsImmunosuppressionImmunosuppression EffectImmunosuppressive EffectImmunotherapyInterferonsKeytrudaLeptomeningesLesionLinkLocationMTS1MTS1 GenesMalignant Breast NeoplasmMalignant CellMalignant NeoplasmsMalignant TumorMammary CancerMammary NeoplasmsMetastasisMetastasizeMetastatic LesionMetastatic MassMetastatic NeoplasmMetastatic Neoplasm to the BrainMetastatic Neoplasm to the CNSMetastatic Neoplasm to the Central Nervous SystemMetastatic TumorMetastatic Tumor to the BrainMetastatic Tumor to the CNSMetastatic Tumor to the Central Nervous SystemMetastatic malignant neoplasm to brainMissionModelingMultimodal TherapyMultimodal TreatmentNational Institutes of HealthNeoplasm MetastasisNeuraxisNon-Polyadenylated RNAPD-1 antibodyPD1 antibodyPSK-J3Pathway interactionsPatientsPhenotypePopulationPre-Clinical ModelPreclinical ModelsPrimary NeoplasmPrimary TumorPrognosisProtocolProtocols documentationPublic HealthRNARNA ExpressionRNA Gene ProductsRepressionResistanceResolutionRibonucleic AcidRoleSYS-TXSamplingSecondary NeoplasmSecondary TumorSequence AlterationSingle cell seqSiteSystemic TherapyT-Cell ActivationT-CellsT-LymphocyteTNBCTP16TSG9ATestingTherapeuticTimeTissuesTranscriptionTreatment FailureTumor CellTumor ExpansionTumor ImmunityUnited States National Institutes of HealthWorkaPD-1aPD1activate T cellsangiogenesisanti programmed cell death 1anti-PD-1anti-PD-1 Abanti-PD-1 antibodiesanti-PD-1 monoclonal antibodiesanti-PD1anti-PD1 Abanti-PD1 antibodiesanti-PD1 monoclonal antibodiesanti-programmed cell death protein 1anti-programmed cell death protein 1 antibodiesanti-programmed death-1 antibodyanti-tumor immunityantiPD-1antitumor immunitybiomarker identificationbrain micrometastasisbreast cancer metastasiscancer cellcancer cell genomecancer complicationcancer geneticscancer genomecancer immunitycancer metastasiscancer microenvironmentcancer typecandidate identificationcdk Proteinscell behaviorcellular behaviorcerebral spinal fluidcheck point blockadecheckpoint blockadechemotherapycombination therapycombined modality treatmentcombined treatmentcomputational toolboxcomputational toolscomputational toolsetcomputerized toolsdevelopmentaldrivingexhaustionexome sequencingexome-seqflow cytophotometrygenetic determinantgenomic alterationidentification of biomarkersidentification of new biomarkersimmune check point blockadeimmune check point inhibitorimmune checkpoint blockadeimmune microenvironmentimmune suppressionimmune suppressive activityimmune suppressive functionimmune therapeutic approachimmune therapeutic interventionsimmune therapeutic regimensimmune therapeutic strategyimmune therapyimmune-based therapiesimmune-based treatmentsimmuno therapyimmunogenicityimmunosuppressive activityimmunosuppressive functionimmunosuppressive microenvironmentimmunosuppressive responseimmunosuppressive tumor microenvironmentimprovedindividuals with breast cancerinnovateinnovationinnovativemalignancymalignant breast tumormammary tumormarker identificationmouse modelmulti-modal therapymulti-modal treatmentmurine modelneoplasm/cancerneoplastic cellnew drug targetnew druggable targetnew pharmacotherapy targetnew therapeutic targetnew therapy targetnovelnovel drug targetnovel druggable targetnovel pharmacotherapy targetnovel therapeutic targetnovel therapy targetp14ARFp16 Genesp16INK4 Genesp16INK4A Genesp16INK4apathwaypatient subclasspatient subclusterpatient subgroupspatient subpopulationspatient subsetspatient subtypespatients with breast cancerpembrolizumabperipheral bloodperson with breast cancerpharmacologicphase 2 trialphase II trialpost treatmentpressureprimary end pointprimary endpointrecruitrefractory cancerresistance mechanismresistantresistant cancerresistant mechanismresolutionsresponseresponse biomarkerresponse markersscRNA sequencingscRNA-seqsingle cell RNA-seqsingle cell RNAseqsingle cell analysissingle cell expression profilingsingle cell next generation sequencingsingle cell sequencingsingle cell technologysingle cell transcriptomic profilingsingle-cell RNA sequencingsocial rolespinal fluidtherapy failurethymus derived lymphocytetranslational opportunitiestranslational potentialtreatment strategytriple-negative breast cancertriple-negative invasive breast carcinomatumortumor cell metastasistumor genometumor immune microenvironmenttumor microenvironmenttumor-immune system interactionsαPD-1αPD1
Description preview
PROJECT SUMMARY
Metastases to the central nervous system (CNS) are a common complication of breast cancer. Prognosis is
typically on the order of a few months. Immunotherapies have revolutionized the management of many types of
cancers. However, these agents have not been systematically studied in the management of CNS metastases
from breast…
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