grant
Effect of DNA repeat silencing on efficacy of ATRi in prostate cancer treatment
Organization UNIVERSITY OF PENNSYLVANIALocation PHILADELPHIA, UNITED STATESPosted 3 Apr 2023Deadline 31 Mar 2028
NIHUS FederalResearch GrantFY2025ATM Gene MutationATM mutationAdenovirus E1A-Associated Protein p60AffectAntioncogene Protein p53BRCA2BRCA2 geneBreast Cancer 2 GeneBreast Cancer Type 2 Susceptibility GeneCDC2CDC2 Protein KinaseCDC2 geneCDK1Cancer TreatmentCancersCausalityCell Cycle Controller CDC2 GeneCell Cycle Controller cdc2Cell Division Control Protein 2 HomologCell Division Cycle 2Cell Division Cycle 2 ProteinCell LineCellLineCellular Tumor Antigen P53ClinicalCombined Modality TherapyComplexCyclin ACyclin-Dependent Kinase 1DNADNA Double Strand BreakDNA Polymerase IIIDNA Polymerase deltaDNA ReplicationDNA Replication InhibitionDNA SequenceDNA StructureDNA SynthesisDNA Synthesis InhibitionDNA biosynthesisDNA mutationDNA replication forkDNA-Dependent DNA Polymerase IIIDefectDeoxyribonucleic AcidDouble Strand Break RepairDrug SynergismDrugsE1A p60Early Onset Gene Breast Cancer 2EtiologyExhibitsFANCD1FosteringFrequenciesGene InactivationGene SilencingGene TranscriptionGenerationsGenetic ChangeGenetic PredispositionGenetic Predisposition to DiseaseGenetic SusceptibilityGenetic TranscriptionGenetic defectGenetic mutationGenetic propensityGenomeGenomicsHereditary Breast Cancer 2HistonesHybridsInherited PredispositionInherited SusceptibilityLocationMalignant CellMalignant Neoplasm TherapyMalignant Neoplasm TreatmentMalignant NeoplasmsMalignant TumorMalignant neoplasm of prostateMalignant prostatic tumorMediatingMedicationMethylationMinisatellite RepeatsMinisatellitesMolecularMultienzyme ComplexesMultimodal TherapyMultimodal TreatmentMutationNon-Polyadenylated RNAOncoprotein p53P53Pharmaceutical PreparationsPhosphoprotein P53Phosphoprotein pp53PlayPol IIIProstate CAProstate CA therapyProstate CancerProstate Cancer therapyProstate malignancyProtein TP53RB1RB1 geneRNARNA ExpressionRNA Gene ProductsRNA ProcessingRepetitive ElementRepetitive RegionsRepetitive SequenceRetroelementsRibonucleic AcidRoleSINEsSMXShort Interspersed DNA Sequence ElementsShort Interspersed ElementShort Interspersed Nucleotide ElementsSimple Repetitive SequenceSiteStrains Cell LinesStructureSulfamethoxazoleSulfamethylisoxazoleSulfisomezoleTP53TP53 geneTRP53TestingTherapeuticTranscriptionTumor Protein p53Tumor Protein p53 GeneVNTRVNTR LociVNTR RegionVNTR SequencesVariable Number of Tandem RepeatsVariable Tandem Repeatsadvanced prostate cancerandrogen independent prostate cancerandrogen indifferent prostate cancerandrogen insensitive prostate cancerandrogen resistance in prostate cancerandrogen resistant prostate canceranti-cancer therapyataxia telangiectasia mutated gene mutationataxia telangiectasia mutated mutationbrca 2 genecancer cellcancer therapycancer-directed therapycastration resistant CaPcastration resistant PCacastration resistant prostate cancercausationcdc2 gene productcdc2+ Proteincdk1 Kinasecombination therapycombined modality treatmentcombined treatmentcultured cell linederepressiondisease causationdrug/agentefficacy testingendonucleaseenzyme complexexperimentexperimental researchexperimental studyexperimentsgene locusgenetic etiologygenetic locusgenetic mechanism of diseasegenetic vulnerabilitygenetically predisposedgenome mutationgenomic locationgenomic locushormone refractory prostate cancerinhibitormalignancymouse modelmulti-modal therapymulti-modal treatmentmurine modelneoplasm/cancernovelp34 Protein Kinasep34 Protein Kinase Genep34(CDC2) Genep34CDC2p53 Antigenp53 Genesp53 Tumor Suppressorprematureprematurityprostate cancer cellprostate cancer resistant to androgenprostate cancer treatmentprostate tumor cellprotein p53replication forkretinoblastoma-1social rolesynergismtranscriptional silencingtreatment strategytumortumor growth
Description preview
PROJECT SUMMARY
Inhibition of the DNA replication checkpoint regulator ATR is a new and promising cancer treatment. ATR
inhibitors (ATRi) function as cancer treatments by causing double-stranded breaks (DSBs) at sites of problematic
DNA replication. Indeed, we have recently demonstrated that structure-forming repetitive DNA sequences
strongly…
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