grant
Mechanistic Insight to Predict and Prevent Nilotinib-Induced Artery Disease
Organization NORTHWESTERN UNIVERSITYLocation CHICAGO, UNITED STATESPosted 1 Aug 2025Deadline 31 Jul 2030
NIHUS FederalResearch GrantFY2025ABL Tyrosine KinaseABL1ABL1 geneAbelson Murine Leukemia Viral Oncogene Homolog 1AccountingAcuteAddressAdjuvantAdverse effectsAmputationAnkleArterial Obstructive DiseasesArterial Obstructive DisorderArterial Occlusive DiseasesArterial Occlusive DisorderArteriesAssayAttenuatedAuxinsBCR geneBCR1BioassayBiochemicalBiologicalBiological AssayBlast CrisisBlast PhaseBlast Phase CMLBlast Phase Chronic Granulocytic LeukemiaBlast Phase Chronic Myelocytic LeukemiaBlast Phase Chronic Myelogenous LeukemiaBlast Phase Chronic Myeloid LeukemiaBlastic Phase CMLBlastic Phase Chronic Granulocytic LeukemiaBlastic Phase Chronic Myelocytic LeukemiaBlastic Phase Chronic Myelogenous LeukemiaBlastic Phase Chronic Myeloid LeukemiaBlood VesselsBrain Vascular DisordersBreakpoint Cluster RegionCRISPRCRISPR approachCRISPR based approachCRISPR methodCRISPR methodologyCRISPR techniqueCRISPR technologyCRISPR toolsCRISPR-CAS-9CRISPR-based methodCRISPR-based techniqueCRISPR-based technologyCRISPR-based toolCRISPR/CAS approachCRISPR/Cas methodCRISPR/Cas systemCRISPR/Cas technologyCRISPR/Cas9CRISPR/Cas9 technologyCardiovascularCardiovascular Body SystemCardiovascular Organ SystemCardiovascular systemCas nuclease technologyCell BodyCell Culture TechniquesCell DifferentiationCell Differentiation processCell LineCellLineCellsCerebrovascular DiseaseCerebrovascular DisordersChemotherapy ProtocolChemotherapy RegimenChemotherapy-Oncologic ProcedureChronic Granulocytic LeukemiaChronic Myelocytic LeukemiaChronic Myelogenous LeukemiaChronic Myeloid LeukemiaClinicalClinical DataClinical TrialsClustered Regularly Interspaced Short Palindromic RepeatsClustered 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 technologyCombination Chemotherapy RegimenDNADataDecision MakingDeoxyribonucleic AcidDiseaseDisorderDoseDrug TherapyDrugsEPH- and ELK-Related Tyrosine KinaseEPH-and ELK-Related KinaseEffector CellEndothelial CellsEphrin Type-A Receptor 8Ephrin Type-A Receptor 8 PrecursorFreedomGWA studyGWASGene ExpressionGene variantGenesGenetic MarkersGenomeGenomicsGenotypeGoalsHeart VascularHematopoietic Cell TumorHematopoietic MalignanciesHematopoietic NeoplasmsHematopoietic Neoplasms including LymphomasHematopoietic TumorHematopoietic and Lymphoid Cell NeoplasmHematopoietic and Lymphoid NeoplasmsHumanImatinibIn VitroIndividualInterventionIntracranial Vascular DiseasesIntracranial Vascular DisordersIschemiaIschemic HeartIschemic Heart DiseaseIschemic myocardiumJTK7KinasesKnowledgeL-SerineLeiomyocyteLibertyMalignant Hematopoietic NeoplasmMapsMedicationMethodsModelingModern ManMyocardial IschemiaNatureOncologyOncology CancerP150PTK InhibitorsPathway interactionsPatientsPeripheralPharmaceutical PreparationsPharmacological TreatmentPharmacotherapyPhenotypePhosphotransferase GenePhosphotransferasesPositionPositioning AttributePredispositionPreventionProcessProtein Tyrosine KinaseProtein Tyrosine Kinase EEKProtein Tyrosine Kinase InhibitorsProtein-Serine KinaseProtein-Serine-Threonine KinasesProtein-Threonine KinaseProto-Oncogene Proteins c-ablProto-Oncogene Tyrosine -Protein Kinase ABLPublicationsQTLQuantitative Trait LociQuimioterapiaRNA SeqRNA sequencingRNAseqRegio tarsalisRiskRisk FactorsRoleSNP arraySNP chipSNP genotypingSafetyScientific PublicationSerineSerine KinaseSerine-Threonine KinasesSerine/Threonine Protein Kinase GeneSmooth Muscle CellsSmooth Muscle MyocytesSmooth Muscle Tissue CellStrains Cell LinesSusceptibilitySystemTK InhibitorsTestingTherapeuticThreonine KinaseToxic effectToxicitiesTransphosphorylasesTyrosineTyrosine KinaseTyrosine Kinase InhibitorTyrosine-Protein Kinase Receptor EEKTyrosine-Specific Protein KinaseTyrosylprotein KinaseVariantVariationVascular DiseasesVascular DisorderVascular Smooth MuscleWorkabl Proto-Oncogene Productsabl Proto-Oncogene Proteinsadverse drug reactionallelic variantattenuateattenuatesbiologicblood cancerblood vessel disorderbrain vascular diseasebrain vascular dysfunctionc-ABL Proteinc-Ablc-abl Genesc-abl Proto-Oncogenescancer chemotherapycancer of bloodcancer of the bloodcandidate identificationcardiac ischemiacardiovascular riskcardiovascular risk factorcase-by-case basiscausal allelecausal genecausal mutationcausal variantcausative mutationcausative variantcell culturecell culturescellular differentiationcerebral vascular diseasecerebral vascular dysfunctioncerebrovascular dysfunctioncirculatory systemcohortcoronary ischemiacultured cell linedifferential expressiondifferentially expresseddisease phenotypedrug interventiondrug treatmentdrug/agententire genomeexperiencefull genomefusion genegene biomarkergene expression biomarkergene markergene signature biomarkergenetic biomarkergenetic variantgenome editinggenome sequencinggenome wide associationgenome wide association scangenome wide association studygenomewide association scangenomewide association studygenomic editinggenomic variantheart ischemiahiPSChuman diseasehuman iPShuman iPSChuman induced pluripotent cellhuman induced pluripotent stem cellshuman inducible pluripotent stem cellshuman inducible stem cellshuman modelhydroxyaryl protein kinaseindexinginduced human pluripotent stem cellsinsightintracranial vascular dysfunctionleukemialeukemia treatmentleukemic therapylogarithmlogarithmicmodel of humanmyocardial ischemia/hypoxiamyocardium ischemianoveloverexpressoverexpressionpathwaypatient responsepatient specific responsepharmaceutical interventionpharmacologicpharmacological interventionpharmacological therapypharmacology interventionpharmacology treatmentpharmacotherapeuticsprecision medicineprecision-based medicinepreventpreventingrecruitresponseresponsive patientscreeningscreeningsside effectsingle nucleotide polymorphism arraysingle nucleotide polymorphism chipsingle nucleotide polymorphism genotypingsocial rolestem cell approachstem cell based approachstem cell methodstem cell methodologystem cell procedurestem cell techniquesuccesstooltranscriptional differencestranscriptome sequencingtranscriptomic sequencingtyrosine kinase ABL1tyrosyl protein kinasevascularvascular dysfunctionvasculopathywhole genomewhole genome association analysiswhole genome association study
Description preview
PROJECT SUMMARY
The BCR-ABL1 tyrosine kinase inhibitor (TKI) nilotinib (Tasigna, Novartis) is the most commonly prescribed
treatment for chronic myelogenous leukemia (CML). The 10-year analysis of the ENESTnd clinical trial (2021)
showed that nilotinib is more effective than its closest competitor imatinib, with 97.3% of patients achieving
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