grant
Defining the oncogenic potential and therapeutic dependencies of PDAC-associated KRAS variants
Organization WEILL MEDICAL COLL OF CORNELL UNIVLocation NEW YORK, UNITED STATESPosted 25 Nov 2024Deadline 30 Nov 2029
NIHUS FederalResearch GrantFY2026Acinar CellAciner CellsAcinus organ componentAnimal ModelAnimal Models and Related StudiesAntioncogene Protein p53Automobile DrivingBehaviorBiologic ModelsBiological ModelsBiologyC-K-RASCDK4ICDKN2CDKN2 GenesCDKN2ACDKN2A geneCMM2Cancer GenesCancer-Promoting GeneCancersCell BodyCell Communication and SignalingCell LineCell LineageCell SignalingCellLineCellsCellular Tumor Antigen P53ChromatinClinicalClinical ResearchClinical StudyCyclin-Dependent Kinase Inhibitor 2A GeneDNA AlterationDNA Sequence AlterationDNA mutationDPC4DataDefectDeleted in Pancreatic CarcinomaDependenceDevelopmentDiagnosisDiseaseDisease ProgressionDisorderDrosophila Homolog of Mothers Against Decapentaplegic 4DuctDuct (organ) structureEngraftmentEpigeneticEpigenetic ChangeEpigenetic MechanismEpigenetic ProcessEpithelial CellsEpitheliumEventExtracellular Signal-Regulated Kinase GeneFoundationsGenesGenetic AlterationGenetic ChangeGenetic defectGenetic mutationINK4INK4AIn VitroIndividualInflammationIntracellular Communication and SignalingIntrinsic factorK-RAS2AK-RAS2BK-RasK-Ras 2AK-Ras-2 OncogeneK-ras mouse modelKPC genetically-engineered mouseKPC modelKPC mouseKPC murineKRASKRAS(G12D)KRAS2KRAS2 geneKRASG12DKi-RASKras mouse modelKras murine modelLSL-KrasG12D/+;LSL-Trp53R172H/+;Pdx-1-CreLSL-KrasG12D/+;LSL-p53R172H/+;Pdx-1-CreLesionLinkMADH4MADH4 geneMAP Kinase GeneMAPKMMAC1MMAC1 proteinMTS1MTS1 GenesMalignant CellMalignant NeoplasmsMalignant Pancreatic NeoplasmMalignant TumorMalignant neoplasm of pancreasMediatingMetaplasiaMetaplastic ChangeMetastasis to Lymph NodesMetastatic Neoplasm to Lymph NodesMetastatic Tumor to Lymph NodesMiceMice MammalsMitogen-Activated Protein Kinase GeneModel SystemMolecularMolecular EvolutionMurineMusMutateMutated in Multiple Advanced Cancers 1MutationNeoplastic Cell TransformationOncogene K-RasOncogenesOncogenicOncoprotein p53OrganoidsOutcomeP53PDAC cancer cellPDAC cellPHTS genePHTS proteinPI-3K/AKTPI3K-AlphaPI3K/AKTPIK3-AlphaPIK3CAPIK3CA genePTENPTEN genePTEN proteinPTEN1PanINPancreasPancreas CancerPancreas Ductal AdenocarcinomaPancreaticPancreatic CancerPancreatic DiseasesPancreatic DisorderPancreatic Duct DysplasiaPancreatic Ductal AdenocarcinomaPancreatic Ductal DysplasiaPancreatic Intraepithelial NeoplasiaPathway interactionsPatient outcomePatient-Centered OutcomesPatient-Focused OutcomesPatientsPatternPhosphatase and Tensin HomologPhosphatase and Tensin Homolog Deleted on Chromosome 10Phosphatidylinositol 3-Kinase, Catalytic, 110-kD, AlphaPhosphatidylinositol 3-Kinase, Catalytic, AlphaPhosphoprotein P53Phosphoprotein pp53ProcessPrognosisProliferatingProtein TP53RASK2RoleRouteSMA- and MAD-Related Protein 4SMAD4SamplingSequence AlterationShapesSignal TransductionSignal Transduction SystemsSignalingStrains Cell LinesT-StageTP16TP53TP53 geneTRP53TSG9ATechnologyTestingTherapeuticTherapeutic InterventionTransforming GenesTransplantationTumor CellTumor PromotionTumor Protein p53Tumor Protein p53 GeneTumor Suppressor ProteinsTumor stageVAV1VAV1 geneVariantVariationWorkacinusbiological signal transductioncancer cellcancer progressioncancer typecell transformationcultured cell linedevelopmentaldrivingeffective therapyeffective treatmentepigeneticallyepigenomegenome mutationgenomic alterationglobal gene expressionglobal transcription profileimprovedin vivointervention therapylymph node metastasismalignancymodel of animalmouse modelmurine modelmutantmutated in multiple advanced cancers 1 proteinneoplasm progressionneoplasm/cancerneoplasticneoplastic cellneoplastic progressionneoplastic transformationnovelp110-Alphap14ARFp16 Genesp16INK4 Genesp16INK4A Genesp16INK4ap53 Antigenp53 Genesp53 Tumor Suppressorpancreas disorderpancreas duct dysplasiapancreas ductal dysplasiapancreatic ductal adenocarcinoma cellpancreatic malignancypathwaypatient oriented outcomespharmacologicphosphatase and tensin homologue on chromosome tenpre-clinical studypreclinical studypreventpreventingprotein p53responseresponse to therapyresponse to treatmentsocial roletargeted drug therapytargeted drug treatmentstargeted therapeutictargeted therapeutic agentstargeted therapytargeted treatmenttherapeutic responsetherapy responsetranscriptometranscriptomicstransformed cellstranslational studytransplanttreatment responsetreatment responsivenesstumortumor growthtumor initiationtumor progressiontumor suppressorunpublished worksv-Ki-RAS2 Kirsten Rat Sarcoma 2 Viral Oncogene Homolog
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PROJECT SUMMARY
Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer, often diagnosed in late stages and with few to
no effective treatment options. Understanding the molecular and cellular changes that drive the genesis of PDAC
will help define therapeutic opportunities to improve clinical outcomes. The current dogma of PDAC initiation…
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