grant
Developing isoform-selective Hsp90 inhibitors for monotherapy and enhanced immunotherapy against lethal prostate cancer
Organization UNIVERSITY OF NOTRE DAMELocation NOTRE DAME, UNITED STATESPosted 10 Jun 2025Deadline 31 May 2030
NIHUS FederalResearch GrantFY2025AddressAffinityAnti-Cancer AgentsAntineoplastic AgentsAntineoplastic DrugsAntineoplasticsBindingBinding SitesCancer Cell GrowthCancer DrugCancer PatientCancer TreatmentCancersCardiac ToxicityCardiotoxicCardiotoxicityCastrationCell Communication and SignalingCell SignalingCell-Mediated Lympholytic CellsChaperoneClientClinicalClinical EvaluationClinical TestingClinical TrialsCombining SiteComplexCytolytic T-CellCytotoxic T CellCytotoxic T-LymphocytesDataDevelopmentDiseaseDisorderDoseDose LimitingDown-RegulationDrugsEarly-Stage Clinical TrialsEffectivenessExhibitsFrequenciesGene ExpressionGenesGoalsHSP 90 inhibitionHSP90 inhibitionHalf-LifeHealthHeat ShockHeat shock proteinsHeat-Shock ReactionHeat-Shock ResponseHumanIFNImmuneImmune mediated therapyImmunesImmunologically Directed TherapyImmunotherapyIn VitroIn vivo analysisInfiltrationInterferonsInterventionIntracellular Communication and SignalingInvestigatorsIsoformsLeadMalignant CellMalignant Neoplasm TherapyMalignant Neoplasm TreatmentMalignant NeoplasmsMalignant TumorMalignant neoplasm of prostateMalignant prostatic tumorMaximal Tolerated DoseMaximally Tolerated DoseMaximum Tolerated DoseMedicationMetabolic Protein DegradationMethodsMiceMice MammalsMissionModern ManMolecular ChaperonesMolecular ConfigurationMolecular ConformationMolecular InteractionMolecular StereochemistryMurineMusMyeloid-derived suppressor cellsN-terminalNH2-terminalNational Institutes of HealthNeoplastic Disease Chemotherapeutic AgentsOncologyOncology CancerOutcomeOutcome StudyPatient outcomePatient-Centered OutcomesPatient-Focused OutcomesPatientsPb elementPermeabilityPharmaceutical PreparationsPhase 1 Clinical TrialsPhase I Clinical TrialsPhotoreceptor CellPhotoreceptorsPhotosensitive CellPlayProcessProliferatingPropertyProstateProstate CAProstate CancerProstate GlandProstate malignancyProstatic GlandProtein IsoformsProtein TurnoverProteinsProteomeQOLQuality of lifeReactive SiteRegulatory Protein DegradationResearchResearch PersonnelResearchersResistanceRoleSafetyScheduleScienceSignal TransductionSignal Transduction SystemsSignalingSolubilitySpecificityStructureSurgical CastrationSurvival RateT cell infiltrationTaxotereTestingTherapeuticTimeToxic effectToxicitiesTumor-Specific Treatment AgentsUnited States National Institutes of HealthViralVisual ReceptorWorkadvanced prostate cancerandrogen independent prostate cancerandrogen indifferent prostate cancerandrogen insensitive prostate cancerandrogen resistance in prostate cancerandrogen resistant prostate canceranti-cancer druganti-cancer therapyaqueousbiological signal transductionbiomarker identificationbonecancer cellcancer microenvironmentcancer progressioncancer therapycancer typecancer-directed therapycastration resistant CaPcastration resistant PCacastration resistant prostate cancercheck point blockadecheckpoint blockadeclinical testcohortconformationconformationalconformational stateconformationallyconformationsdetermine efficacydevelopmentaldocetaxeldocetaxoldrug candidatedrug developmentdrug/agenteffective therapyeffective treatmentefficacy analysisefficacy assessmentefficacy determinationefficacy evaluationefficacy examinationevaluate efficacyexamine efficacyeye toxicityheat shock protein 90 inhibitionheavy metal Pbheavy metal leadhormone refractory prostate canceridentification of biomarkersidentification of new biomarkersimmune check point blockadeimmune checkpoint blockadeimmune therapeutic approachimmune therapeutic interventionsimmune therapeutic regimensimmune therapeutic strategyimmune therapyimmune-based therapiesimmune-based treatmentsimmuno therapyimmunogenicityimmunosuppressive myeloid cellsimprovedin vivoin vivo evaluationin vivo testinginhibitorinhibitor druginhibitor therapeuticinhibitor therapykiller T cellmalignancymarker identificationmimicrymyeloid suppressor cellsmyeloid-derived suppressive cellsnano-molarnanomolarneoplasm progressionneoplasm/cancerneoplastic progressionnew approachesnew drug treatmentsnew drugsnew pharmacological therapeuticnew therapeuticsnew therapynext generation therapeuticsnovelnovel approachesnovel drug treatmentsnovel drugsnovel pharmaco-therapeuticnovel pharmacological therapeuticnovel strategiesnovel strategynovel therapeuticsnovel therapyocular toxicityoverexpressoverexpressionpatient oriented outcomespharmacologicphase I protocolpreservationprostate cancer cellprostate cancer cell lineprostate cancer modelprostate cancer resistant to androgenprostate tumor cellprostate tumor modelprotein degradationrefractory cancerresearch clinical testingresistantresistant cancerresponseretinal toxicityside effectsocial rolestress proteinsuccesssuppressive myeloid cellssynergismtraffickingtreatment strategytumortumor eradicationtumor microenvironmenttumor progression
Description preview
PROJECT SUMMARY/ABSTRACT
This project focuses on pioneering a novel approach in anti-cancer drug development through the
creation and optimization of isoform-selective inhibitors targeting the 90 kDa heat shock protein (Hsp90β). Hsp90
is a crucial chaperone protein involved in the maturation of over 400 client proteins, many of which play…
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