grant
The role of USP27X-Cyclin D1 axis in HER2 Therapy Resistant Breast Cancer
Organization ROSWELL PARK CANCER INSTITUTE CORPLocation BUFFALO, UNITED STATESPosted 26 Apr 2023Deadline 31 Mar 2028
NIHUS FederalResearch GrantFY2025APF-1ATP-Dependent Proteolysis Factor 1AblationAccelerationAffectAllelesAllelomorphsAnti-ERB-2Anti-HER2/c-erbB2 Monoclonal AntibodyAnti-c-ERB-2Anti-c-erbB2 Monoclonal AntibodyAnti-erbB-2Anti-erbB2 Monoclonal AntibodyAnti-p185-HER2Antibody-drug conjugatesBiochemicalBreast CancerBreast Cancer CellBreast Cancer PatientBreast Cancer cell lineBreast Tumor PatientBreast tumor cell lineCCND1 ProteinCDK4CDK4 geneCRISPR approachCRISPR based approachCRISPR methodCRISPR methodologyCRISPR techniqueCRISPR technologyCRISPR toolsCRISPR-CAS-9CRISPR-based methodCRISPR-based techniqueCRISPR-based technologyCRISPR-based toolCRISPR/CAS approachCRISPR/Cas methodCRISPR/Cas technologyCRISPR/Cas9CRISPR/Cas9 technologyCancer ModelCancer PatientCancer cell lineCancerModelCancersCas nuclease technologyCell BodyCell Division Kinase 4Cell Growth in NumberCell LineCell MultiplicationCell ProliferationCellLineCellsCellular ExpansionCellular GrowthCellular ProliferationClinicalClustered Regularly Interspaced Short Palindromic Repeats approachClustered Regularly Interspaced Short Palindromic Repeats methodClustered Regularly Interspaced Short Palindromic Repeats methodologyClustered Regularly Interspaced Short Palindromic Repeats techniqueClustered Regularly Interspaced Short Palindromic Repeats technologyCyclin D1Cyclin-Dependent Kinase 4DataDedicationsDeubiquitinating EnzymeDeubiquitinationDevelopmentDrug TargetingDrug resistanceEGF ReceptorEGFRERBB ProteinERBB2ERBB2 geneEngineeringEnzyme GeneEnzymesEpidermal Growth Factor ReceptorEpidermal Growth Factor Receptor KinaseEpidermal Growth Factor Receptor Protein-Tyrosine KinaseEpidermal Growth Factor-Urogastrone ReceptorsFamilyFosteringG1/S-Specific Cyclin D1Gene Action RegulationGene Expression RegulationGene RegulationGene Regulation ProcessGene TranscriptionGenetic TranscriptionHER -2HER-2HER-2 inhibitionHER1HER2HER2 GenesHER2 Monoclonal AntibodyHER2 inhibitionHER2/neuHMG-20HandHerceptinHigh Mobility Protein 20HistonesHumanLoxP-flanked alleleMalignant Breast NeoplasmMalignant CellMalignant NeoplasmsMalignant TumorMediatingMiceMice MammalsMoAb HER2Modern ManMolecularMolecular AnalysisMurineMusNEU OncogeneNEU proteinOncogene ErbB2OncogenesisPRAD1 ProteinPSK-J3PTK InhibitorsPathway interactionsPatientsPhenotypeProcessProtein Tyrosine Kinase InhibitorsProteinsProto-Oncogene Proteins c-bcl-1RNA ExpressionRecurrenceRecurrentRegulationResistanceRoleStrains Cell LinesTGF-alpha ReceptorTK InhibitorsTKR1TamoxifenTestingTherapeutic InterventionTranscriptionTransforming Growth Factor alpha ReceptorTrastuzumabTumor CellTumor EscapeTumor Immune EscapeTumorigenicityTyrosine Kinase InhibitorUbiquitinUrogastrone ReceptorWorkXenograft Modelbcl-1 Proto-Oncogene Productsbcl-1 Proto-Oncogene Proteinsbcl1 Proto-Oncogene Proteinsbreast tumor cellc-bcl-1 Proteinsc-erb-2 Monoclonal Antibodyc-erbB-1c-erbB-1 Proteinc-erbB-2c-erbB-2 Genesc-erbB-2 Proto-Oncogenescancer cellcancer evasioncancer immune escapecancer immune evasioncancer survivalcell growthclinical relevanceclinically relevantcultured cell linecyclin Dde-ubiquitinasede-ubiquitinating enzymedevelopmentaldrug resistantdruggable targeterbB-1erbB-1 Proto-Oncogene ProteinerbB-2 GeneserbBlfloxedfloxed allelegenetic approachgenetic strategyhandsherstatinimprovedin vivoindividuals with breast cancerinduced Creinducible Creinhibitorinsightintervention therapymalignancymalignant breast tumormembermouse modelmurine modelneoplasm/cancerneoplastic cellneu Genesnoveloverexpressoverexpressionpathwaypatient prognosispatients with breast cancerperson with breast cancerproto-oncogene protein c-erbB-1resistance mechanismresistance to Drugresistance to therapyresistantresistant mechanismresistant to Drugresistant to therapyresponseresponse to therapyresponse to treatmentrhuMAb HER2shRNAshort hairpin RNAsmall hairpin RNAsocial roletargeted agenttargeted drug therapytargeted drug treatmentstargeted therapeutictargeted therapeutic agentstargeted therapytargeted treatmenttherapeutic resistancetherapeutic responsetherapeutic targettherapy resistanttherapy responsetreatment resistancetreatment responsetreatment responsivenesstumortumor evasiontumor growthtumor immune evasiontumor xenografttumorigenesisubiquitin isopeptidaseubiquitin-specific isopeptidaseubiquitin-specific proteasexenograft transplant modelxenotransplant model
Description preview
PROJECT SUMMARY/ABSTRACT
Overexpression of Cyclin D1 (CCND1) is recognized as a major resistance mechanism to HER2 targeting
agents. Patients with CCND1 amplification have the worst response to trastuzumab-containing therapy, and
CCND1 overexpression is enough to render cancer cells insensitive to HER2 inactivation. Furthermore, tumors
that evade…
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