grant
Homologous recombination repair pathway mutations and genetic mechanisms shaping anti-tumor immunity and immunotherapy efficacy
Organization CLEVELAND CLINIC LERNER COM-CWRULocation CLEVELAND, UNITED STATESPosted 1 Aug 2025Deadline 31 Jul 2030
NIHUS FederalResearch GrantFY2025AbscissionAffectAfter CareAfter-TreatmentAftercareAnimal ModelAnimal Models and Related StudiesAntibodiesAreaBRCA1BRCA1 Gene ProductBRCA1 MutationBRCA1 ProteinBRCA1 geneBRCA1 gene mutationBRCA2BRCA2 MutationBRCA2 geneBRCA2 gene mutationBiological Response ModifiersBiomodulatorsBreast Cancer 1 GeneBreast Cancer 1 Gene ProductBreast Cancer 2 GeneBreast Cancer Type 1 Susceptibility GeneBreast Cancer Type 1 Susceptibility ProteinBreast Cancer Type 2 Susceptibility GeneBreast-Ovarian Cancer ProteinCDS1CHEK2CHEK2 geneCHK2Cancer PatientCancersCds1 kinaseCell BodyCellsChk2 protein kinaseCytosolDNA AlterationDNA DamageDNA Damage RepairDNA InjuryDNA RepairDNA Repair PathwayDNA Sequence AlterationDNA mutationDataDefectEarly Onset Gene Breast Cancer 1Early Onset Gene Breast Cancer 2Early Onset Protein Breast Cancer 1EvaluationExcisionExtirpationFANCD1FoundationsGenerationsGenesGeneticGenetic AlterationGenetic ChangeGenetic defectGenetic mutationGenomicsGoalsHereditary Breast Cancer 1Hereditary Breast Cancer 2Homologous Recombinational RepairHumanHuman GeneticsImmune MediatorsImmune Mediators/ModulatorsImmune mediated therapyImmune responseImmune signalingImmune systemImmunochemical ImmunologicImmunogenomicsImmunologicImmunologicalImmunologicallyImmunologically Directed TherapyImmunologicsImmunologyImmunotherapyIndividualInflammasomeInnate ImmunityInterdisciplinary ResearchInterdisciplinary StudyLeadMalignant NeoplasmsMalignant TumorMediatingMismatch RepairModelingModern ManMolecularMultidisciplinary CollaborationMultidisciplinary ResearchMutagenic ProcessMutateMutationNative ImmunityNatural ImmunityNon-Specific ImmunityNonspecific ImmunityNucleic AcidsOutcomePALB2PALB2 genePD-1 antibodyPD-1 antibody therapyPD-1 therapyPD-1/PD-L1PD-1/PDL1PD1 antibodyPD1 antibody therapyPD1 based treatmentPD1-PD-L1PD1/PD-L1PD1/PDL1PP1425Pathologic MutagenesisPathologic Mutagenic ProcessPathway interactionsPatientsPb elementPost-Replication Mismatch RepairProcessRAD51CRAD51C geneRAD53RNF53Recombination RepairRemovalResearchResistanceSamplingSequence AlterationShapesSingle cell seqStimulator of Interferon GenesSurgical RemovalT-CellsT-LymphocyteTestingTherapeuticTumor CellTumor ImmunityUnscheduled DNA SynthesisWorkaPD-1aPD-1 therapyaPD-1 treatmentaPD1aPD1 therapyaPD1 treatmentadaptive immunityanti programmed cell death 1anti-PD-1anti-PD-1 Abanti-PD-1 antibodiesanti-PD-1 monoclonal antibodiesanti-PD-1 therapyanti-PD-1 treatmentanti-PD1anti-PD1 Abanti-PD1 antibodiesanti-PD1 monoclonal antibodiesanti-PD1 therapyanti-PD1 treatmentanti-cancer immunotherapyanti-programmed cell death 1 therapyanti-programmed cell death protein 1anti-programmed cell death protein 1 antibodiesanti-programmed cell death protein 1 therapyanti-programmed death-1 antibodyanti-tumor effectanti-tumor immune therapyanti-tumor immunityanti-tumor immunotherapyantiPD-1anticancer immunotherapyantitumor effectantitumor immunitybrca 1 genebrca 2 genecGAMP STINGcGAMP-STINGcGAMP/STINGcGAS/STINGcancer immunitycancer immunotherapycancer microenvironmentcancer progressioncancer typecheck point blockadecheck point kinase 2checkpoint blockadecheckpoint kinase 2cohortcyclic GMP-AMP synthase/STINGdesigndesigningdifferential expressiondifferentially expressedgenome mutationgenomic alterationheavy metal Pbheavy metal leadhomologous recombinationhomologous recombination deficiencyhomologous recombination repair deficiencyhost responseimmune check point blockadeimmune checkpoint blockadeimmune system responseimmune therapeutic approachimmune therapeutic interventionsimmune therapeutic regimensimmune therapeutic strategyimmune therapyimmune-based cancer therapiesimmune-based therapiesimmune-based treatmentsimmuno therapyimmunogenicityimmunoresponseimmunotherapy for cancerimmunotherapy of cancerimprovedinsightmalignancymodel of animalmouse modelmurine modelmutantneo-antigenneo-epitopesneoantigensneoepitopesneoplasm immunotherapyneoplasm progressionneoplasm/cancerneoplastic cellneoplastic progressionnew drug targetnew druggable targetnew pharmacotherapy targetnew therapeutic targetnew therapy targetnovel drug targetnovel druggable targetnovel pharmacotherapy targetnovel therapeutic targetnovel therapy targetpartner and localizer of BRCA2pathwaypost treatmentpredictive biological markerpredictive biomarkerspredictive markerpredictive molecular biomarkerprogrammed cell death protein 1 therapyrecombinational repairrepairrepairedresectionresistantresponseresponse to therapyresponse to treatmentserine-threonine-protein kinase Chk2single cell next generation sequencingsingle cell sequencingtherapeutic responsetherapy responsethymus derived lymphocytetranscriptional differencestreatment responsetreatment responsivenesstumortumor eradicationtumor immune therapytumor immunotherapytumor microenvironmenttumor progressionαPD-1αPD1
Description preview
PROJECT SUMMARY
Immune checkpoint blockade (ICB) therapies such as PD1/PD-L1-targeting antibodies activate the
immune system to help eradicate tumor cells. However, treatment response varies dramatically across patients
and cancer types. Genetic defects in DNA damage response pathways predispose to cancer and strongly
influence tumor immunity.…
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