grant
Drug Mechanism of Action-based targeting of tumor subpopulations
Organization COLUMBIA UNIVERSITY HEALTH SCIENCESLocation NEW YORK, UNITED STATESPosted 19 Sept 2023Deadline 31 Aug 2028
NIHUS FederalResearch GrantFY2025AbscissionAddressAlgorithmsBehaviorC1 qC1qCancer CenterCancer PatientCancersCell BodyCell LineCell modelCellLineCellsCellular modelCheckpoint inhibitorClinicalComplement 1qComplement C1qComplexDataDependenceDisease-Free SurvivalDrug TargetingDrug TherapyDrug resistanceDrugsDuctDuct (organ) structureEvent-Free SurvivalExcisionExtirpationExtracellular Signal-Regulated Kinase GeneFibroblastsFosteringFundingGEM modelGEMM modelGenetically Engineered MouseGoalsHealthHeterogeneityHumanImmuneImmune checkpoint inhibitorImmune mediated therapyImmune responseImmunesImmunologically Directed TherapyImmunosuppressionImmunosuppression EffectImmunosuppressive EffectImmunotherapyIn VitroIndividualInfiltrationInter-tumoral heterogeneityIntratumoral heterogeneityIsogeneic HomograftIsogeneic TransplantationIsogenic transplantationIsograftKPC genetically-engineered mouseKPC modelKPC mouseKPC murineLSL-KrasG12D/+;LSL-Trp53R172H/+;Pdx-1-CreLSL-KrasG12D/+;LSL-p53R172H/+;Pdx-1-CreLogicMAP Kinase GeneMAPKMacrophageMalignantMalignant - descriptorMalignant CellMalignant NeoplasmsMalignant TumorMediatingMedicationMetaplasiaMetaplastic ChangeMethodologyMitogen-Activated Protein Kinase GeneModelingModern ManMolecularMφNetwork-basedNeuroendocrineNeuroendocrine SystemNeurosecretory SystemsOrganoidsOutcomePDX modelPancreas Ductal AdenocarcinomaPancreatic Ductal AdenocarcinomaParacrine CommunicationParacrine SignalingPathway interactionsPatient derived xenograftPatientsPharmaceutical PreparationsPharmacological TreatmentPharmacotherapyPre-Clinical ModelPreclinical ModelsPrediction of Response to TherapyPrintingProteinsProteomePublicationsReagentRegulatory T-LymphocyteRelapseRemovalSamplingScientific PublicationStrains Cell LinesSurgical RemovalSyngeneic HomograftSyngeneic TransplantationSystemTREM2TREM2 geneTherapeuticTregTriggering Receptor Expressed in Myeloid Cells 2Triggering Receptor Expressed on Myeloid Cells 2Tumor CellValidationactionable mutationactionable variantsandrogen independent prostate cancerandrogen indifferent prostate cancerandrogen insensitive prostate cancerandrogen resistance in prostate cancerandrogen resistant prostate cancercancer cellcancer microenvironmentcastration resistant CaPcastration resistant PCacastration resistant prostate cancercell behaviorcellular behaviorcheck point blockadecheckpoint blockadeclinical relevanceclinically relevantcultured cell linedesigndesigningdrug interventiondrug mechanismdrug resistantdrug sensitivitydrug treatmentdrug-sensitivedrug/agentgenetically engineered mouse modelgenetically engineered murine modelgenome databasegenome scalegenome-widegenomewideheterogeneity in tumorshormone refractory prostate cancerhost responsehuman modelimmune check point blockadeimmune check point inhibitorimmune checkpoint blockadeimmune microenvironmentimmune suppressionimmune suppressive activityimmune suppressive functionimmune system responseimmune therapeutic approachimmune therapeutic interventionsimmune therapeutic regimensimmune therapeutic strategyimmune therapyimmune-based therapiesimmune-based treatmentsimmuno therapyimmunoresponseimmunosuppressive activityimmunosuppressive functionimmunosuppressive microenvironmentimmunosuppressive responseimmunosuppressive tumor microenvironmentimprovedin vivo Modelintertumoral heterogeneityintra-tumoral heterogeneityintratumor heterogeneitymalignancymodel of humanneoplasm/cancerneoplastic cellnovelpanaceapathwaypatient derived xenograft modelpatient responsibilitiespharmaceutical interventionpharmacologicpharmacological interventionpharmacological therapypharmacology interventionpharmacology treatmentpharmacotherapeuticspredict therapeutic responsepredict therapy responseprogramsprostate cancer resistant to androgenrecruitregulatory T-cellsrelapse patientsresectionresistance to Drugresistant to Drugresponsesingle cell analysissmall molecular inhibitorsmall molecule inhibitortargeted drug therapytargeted drug treatmentstargeted therapeutictargeted therapeutic agentstargeted therapytargeted treatmenttherapy predictiontreatment predictiontreatment response predictiontumortumor heterogeneitytumor immune microenvironmenttumor microenvironmenttumor-immune system interactionsvalidationsvirtual
Description preview
Patients with aggressive cancers often present with no pharmacologically actionable mutations and fail to
respond to immune checkpoint blockade, thus deriving only modest improvement in disease-free survival from
targeted therapy and immunotherapy. Tumor heterogeneity further complicates these challenges by fostering
paracrine signal-mediated…
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