grant
Functional Characterization and Development of Therapeutic Paradigms for DNA Damage Repair (DDR)-deficient Lethal Prostate Cancer
Organization ICAHN SCHOOL OF MEDICINE AT MOUNT SINAILocation NEW YORK, UNITED STATESPosted 1 Apr 2023Deadline 31 Mar 2028
NIHUS FederalResearch GrantFY2025AddressAndrogen ReceptorAntigen TargetingBRCA2BRCA2 MutationBRCA2 geneBRCA2 gene mutationBiometricsBiometryBiostatisticsBreast Cancer 2 GeneBreast Cancer Type 2 Susceptibility GeneCAR T cell therapyCAR T cellsCAR T therapyCAR modified T cellsCAR-TCAR-TsCRISPR activationCRISPR activatorCRISPR based activationCRISPR editing screenCRISPR gene activationCRISPR screenCRISPR transcription activationCRISPR transcriptional activationCRISPR-Cas-9-mediated gene activationCRISPR-based gene activationCRISPR-based screenCRISPR-dCAS9 ActivatorCRISPR-mediated transcriptional activationCRISPR/CAS9 activationCRISPR/CAS9 gene activationCRISPR/Cas9 screenCRISPR/dCas9 activationCRISPR/dCas9-based transcriptional activationCRISPRaCancer BiologyCancer CauseCancer EtiologyCancer PatientCaringCastrate sensitive prostate cancerCastrationCell BodyCellsCellular biologyCessation of lifeClinicalClinical OncologyClinical TrialsClinical Trials DesignCombined Modality TherapyDNA AlterationDNA Damage RepairDNA Double Strand BreakDNA RepairDNA Sequence AlterationDNA mutationDataDeathDevelopmentDisciplineDiseaseDisorderEarly Onset Gene Breast Cancer 2EpidemiologyExhibitsFANCD1FOLHFOLH1FOLH1 geneFolate Hydrolase 1FoundationsGCP2Gene AlterationGene MutationGenesGenetic AlterationGenetic ChangeGenetic defectGenetic mutationGenome InstabilityGenomic InstabilityGlutamate Carboxypeptidase IIGoalsHereditary Breast Cancer 2HeterozygoteImmune mediated therapyImmunologically Directed TherapyImmunologyImmunotherapyIndolentInduced DNA AlterationInduced MutationInduced Sequence AlterationInvestigatorsKnock-outKnockoutLesionLinkMalignant neoplasm of prostateMalignant prostatic tumorMolecularMultimodal TherapyMultimodal TreatmentMutationN-Acetylated Alpha-Linked Acidic Dipeptidase 1NAALAD1NAALADase IOrganoidsPARP InhibitorPARP inhibitionPARP-1 inhibitorPARPiPSMPSMAPathologyPatientsPoly(ADP-ribose) Polymerase InhibitorPoly(ADP-ribose) polymerase 1 inhibitorPre-Clinical ModelPreclinical ModelsProcessPrognosisProstate CAProstate CA therapyProstate CancerProstate Cancer therapyProstate malignancyProstate-Specific Membrane AntigenRadiation ChemistryRadiation therapyRadiochemistryRadiotherapeuticsRadiotherapyReportingResearch PersonnelResearchersResistanceRoleSequence AlterationSignal PathwaySurgical CastrationT cells for CARTargeted RadiotherapyTestingTherapeuticTimeTranscriptional ControlTranscriptional RegulationTreatment FailureUnscheduled DNA SynthesisUpregulationWorkactivating CRISPR technologyandrogen ablation therapyandrogen blockade therapyandrogen deprivation therapyandrogen deprivation treatmentandrogen independent prostate cancerandrogen indifferent prostate cancerandrogen insensitive prostate cancerandrogen resistance in prostate cancerandrogen resistant prostate cancerandrogen sensitive prostate cancerbrca 2 genecastration resistant CaPcastration resistant PCacastration resistant prostate cancercell biologychimeric antigen T cell receptorchimeric antigen receptor (CAR) T cell therapychimeric antigen receptor (CAR) T cellschimeric antigen receptor Tchimeric antigen receptor T cell therapychimeric antigen receptor T cellschimeric antigen receptor T therapychimeric antigen receptor fusion protein T-cellschimeric antigen receptor modified T cellsclustered regularly interspaced short palindromic repeats screencohortcombination therapycombined modality treatmentcombined treatmentdevelopmentaleffective therapyeffective treatmentefficacy studyepidemiologicepidemiologicalgain of functiongene defectgene repairgenome mutationgenomic alterationheterozygosityhormone refractory prostate cancerhormone sensitive prostate cancerimmune therapeutic approachimmune therapeutic interventionsimmune therapeutic regimensimmune therapeutic strategyimmune therapyimmune-based therapiesimmune-based treatmentsimmuno therapyimmunogenicin vivoinsightloss of functionmenmortalitymulti-modal therapymulti-modal treatmentmutant allelenovelpharmacologicpre-clinicalpreclinicalprogramsprospectiveprostate cancer cellprostate cancer cell lineprostate cancer progressionprostate cancer resistant to androgenprostate cancer treatmentprostate tumor cellradiation treatmentrational designreceptor functionresistance to therapyresistantresistant to therapyresponsesocial rolesynergismtargeted drug therapytargeted drug treatmentstargeted therapeutictargeted therapeutic agentstargeted therapytargeted treatmenttherapeutic agent developmenttherapeutic developmenttherapeutic resistancetherapy failuretherapy resistanttreatment resistancetreatment strategytreatment with radiationtumor
Description preview
Abstract
A leading contributor to the significant mortality burden of prostate cancer, the second cause of cancer death
among U.S. men, is the short-lived efficacy of androgen deprivation therapy (ADT), the mainstay of care for
advanced and symptomatic disease. Increasingly alterations in DNA damage repair (DDR) genes,
predominantly BRCA2, have…
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