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Molecular Imaging Reagents for Prostate Cancer Theranostics

Molecular Imaging Reagents for Prostate Cancer Theranostics
用于前列腺癌治疗诊断的分子成像试剂
批准号:
10226208
负责人:
Zaver M. Bhujwalla
金额:
$23.65万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2017
资助国家:
美国
项目状态:
已结题
起止时间:
2017-09-15 至 2024-06-30
关键词:
AntibodiesAntigen TargetingAutoimmunityBiological SciencesBiopsy SpecimenCTLA4 geneCancer DetectionCancer EtiologyCastrationCause of DeathCellsCessation of lifeClinicalCollagenCollagen FiberComplexCytosine deaminaseDesmoplasticDevelopmentDiagnosisDiseaseDisease ResistanceDown-RegulationEnzymesEstersExtracellular MatrixFOLH1 geneFiberFibroblastsFlucytosineFluorouracilFocal Adhesion Kinase 1Focal AdhesionsFunding MechanismsFutureGoalsImageImmune responseImmune systemImmunosuppressionImmunotherapyInfectionIntegral Membrane ProteinIntegrinsInterferonsInvadedLabelMalignant NeoplasmsMalignant neoplasm of prostateMechanicsMetastatic Prostate CancerMetastatic toMolecularMolecular TargetMonoclonal AntibodiesMovementNeoplasm MetastasisOptical reporterOpticsPathway interactionsPatient SelectionPatientsPhenotypePhototherapyPlayPositron-Emission TomographyProdrugsProstate-Specific AntigenReagentRecurrenceReporterResistanceResourcesRoleSignaling ProteinSiteSmall Interfering RNASourceStromal CellsSurface of the ProstateT-LymphocyteTissuesTranslationsValidationVisualizationantibody conjugatebasecancer cellcancer imagingcancer therapycell killingcell motilitycheckpoint inhibitionclinical translationclinically translatableeffective therapyextracellularfrontierimaging agentimaging modalityimaging platformimaging probeimmune activationimmune checkpointimprovedin vivokinase inhibitormechanotransductionmenmolecular imagingmortalitynanoparticlenanoparticle deliverynoveloverexpressionpre-clinicalprecision medicineprecision oncologyprogrammed cell death ligand 1programmed cell death protein 1prostate cancer metastasisprostate cancer progressionprototyperesponsesuccesstheranosticstreatment trialtumortumor microenvironmenttumor progression

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中文摘要
翻译
TR&D 1总结
英文摘要
SUMMARY for TR&D 1 Prostate cancer (PCa) is the second leading cause of death from cancer in men in the U.S. The vast majority of men dying of PCa continue to succumb to metastatic castration-resistant disease. There is a compelling need to find effective treatments for metastatic PCa. Our purpose in TR&D1 of the BTRC is to successfully develop prototype theranostic molecular imaging platforms to pursue novel avenues of (i) detecting and targeting the focal adhesion kinase (FAK) mechanotransduction pathway that allow cells to migrate (Aims 1a and b), (ii) detecting and eliminating activated cancer associated fibroblasts (CAFs) that play an important role in the formation of a prometastatic extracellular matrix (ECM) in PCa (Aim 2), and (iii) developing prostate specific antigen (PSMA)-targeted nanoparticles (NPs) to deliver siRNA to downregulate programmed death ligand 1 (PD- L1) together with a prodrug enzyme, to exploit the activation of the immune system, together with localized cell killing, in locally advanced and metastatic PCa (Aim 3). Optical and PET imaging reporters will be integrated into the platforms to achieve spatial and temporal visualization of the NPs in vivo for precision medicine. PSMA, a type II integral membrane protein that is abundantly expressed on the surface of PCa in castration-resistant, advanced and metastatic disease, provides a unique advantage to deliver PSMA-specific NPs for effective control and treatment of locally advanced or metastatic PCa. These studies will result in the accelerated development of FAK PET imaging probes with near term clinical translation that will have a direct impact on the selection of patients for ongoing FAK inhibitor treatment trials. Mechanical movement of cancer cells is a prerequisite for invasion and metastasis. NPs that achieve PCa-specific downregulation of FAK using PSMA- specific delivery will provide cancer-specific downregulation of cell migration, a key step in the metastatic cascade. Similarly, detection of CAFs in tumors with imaging will provide a distinct advantage over biopsy specimens in evaluating CAF numbers as a marker of aggressiveness. CAF elimination with phototherapy may provide a strategy to reduce or eliminate PCa metastasis. The development of NPs to improve immunotherapy in PCa through theranostics and their translation will represent a significant advance in this field since PCa has traditionally not responded well to immunotherapy. TR&D1 will also serve as the Pre-Clinical Validation Core that will, through close interactions with the CPs and other TR&Ds, develop and disseminate novel molecular imaging theranostic agents that will advance precision medicine of cancer worldwide.
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The Tumor Microenvironment in Nanoparticle Delivery and Function
  • 批准号:
    10059035
  • 项目类别:
  • 资助金额:
    $37.46万
  • 财政年份:
    2020
  • 负责人:
    Zaver M. Bhujwalla
  • 依托单位:
The Tumor Microenvironment in Nanoparticle Delivery and Function
  • 批准号:
    10405098
  • 项目类别:
  • 资助金额:
    $36.71万
  • 财政年份:
    2020
  • 负责人:
    Zaver M. Bhujwalla
  • 依托单位:
The Tumor Microenvironment in Nanoparticle Delivery and Function
  • 批准号:
    10170305
  • 项目类别:
  • 资助金额:
    $37.46万
  • 财政年份:
    2020
  • 负责人:
    Zaver M. Bhujwalla
  • 依托单位:
The Tumor Microenvironment in Nanoparticle Delivery and Function
  • 批准号:
    10617333
  • 项目类别:
  • 资助金额:
    $36.71万
  • 财政年份:
    2020
  • 负责人:
    Zaver M. Bhujwalla
  • 依托单位:
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