Exosomes in Cancer Therapy
外泌体在癌症治疗中的应用
基本信息
- 批准号:9230198
- 负责人:
- 金额:$ 38.41万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-12-27 至 2021-11-30
- 项目状态:已结题
- 来源:
- 关键词:ApoptosisApplications GrantsBiological AssayBiologyBlood CirculationBrainCD47 geneCell ProliferationCellsClinicClinicalCodon NucleotidesComplementCoupledCultured CellsDNADataDiseaseEatingElectroporationEndopeptidase KEngineeringExhibitsExtracellular ProteinFibroblastsFrequenciesFutureGeneticGenetic studyGenetically Engineered MouseGlycineHalf-LifeHumanITGAM geneImageImpairmentIntegrinsInvestigationKRAS2 geneLabelLiposomesLiverLungMalignant NeoplasmsMalignant neoplasm of pancreasMediatingMediator of activation proteinMolecularMusMutationOncogenicPancreasPancreatic Ductal AdenocarcinomaPathogenesisPathway interactionsPatientsPerformancePhagocytesPharmaceutical PreparationsPharmacologyPhysiologicalPlayProcessProteinsProteomicsRNARNA InterferenceResearchRoleRouteSignal TransductionSmall Interfering RNASurvival RateSystemTechniquesTertiary Protein StructureTestingTherapeuticTissuesTrypsinWestern BlottingXenograft procedurebasecancer therapydesigndosageeffective therapyexosomeexperimental studyextracellular vesiclesimaging modalityimprovedinsightknowledge translationmacrophagemonocytemouse modelnanoparticleneutralizing antibodynovel strategiesnovel therapeuticsoutcome forecastpancreatic cancer cellspancreatic neoplasmpenis foreskinpre-clinicalpreclinical studyprogramssmall hairpin RNAstandard of caretherapeutic evaluationtumortumor progression
项目摘要
Pancreatic Ductal Adenocarcinoma (PDAC) has a dismal prognosis with a median survival of about 6 months
for patients with metastatic disease despite the use of current treatments. Therefore, PDAC is in urgent need
of effective therapies. About 80% of PDAC patients exhibit mutation in KRAS, with substitution of a glycine
residue at codon 12, such as KRASG12D, observed in high frequency. Many studies in mice unequivocally show
that direct inhibition oncogenic KRAS significantly suppresses tumor progression. Despite such compelling
evidence for the functional role of oncogenic KRAS in the PDAC pathogenesis, direct targeting of oncogenic
KRAS has been elusive and it has often been dubbed as ‘undruggable’. In this grant application, we propose to
explore a novel approach to target oncogenic KRAS using physiological nanoparticles known as exosomes.
Exosomes are 40-150 nm extracellular vesicles (EVs) that contain DNA, RNA and proteins, and can deliver
their contents efficiently into cells they fuse with and/or enter. Exploiting this unique feature of exosomes, our
research team proposes in this grant application to test the central hypothesis that ‘exosomes can be
engineered to deliver RNA interference (RNAi) molecules to target KRASG12D in pancreatic cancer’.
Successful completion of the proposed studies will determine whether exosomes exhibit a superior ability to
deliver RNAi molecules for the treatment of pancreatic cancer when compared to liposomes. Additionally, after
such increased ability is investigated using multiple experimental systems, the proposal will further identify
mechanism/s associated with the enhanced efficacy of exosomes in the delivery of RNAi molecules.
Collectively, the proposal is designed to enable in-depth pre-clinical studies coupled with an investigation into
the unique mechanism of action of exosomes to potentially facilitate future therapeutic testing in patients with
PDAC.
胰腺导管腺癌(PDAC)预后不佳,中位生存期约为6个月
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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RAGHU KALLURI其他文献
RAGHU KALLURI的其他文献
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{{ truncateString('RAGHU KALLURI', 18)}}的其他基金
Mechanisms associated with organotropic metastasis
与器官转移相关的机制
- 批准号:
10295926 - 财政年份:2021
- 资助金额:
$ 38.41万 - 项目类别:
Mechanisms associated with organotropic metastasis
与器官转移相关的机制
- 批准号:
10439900 - 财政年份:2021
- 资助金额:
$ 38.41万 - 项目类别:
Mechanisms associated with organotropic metastasis
与器官转移相关的机制
- 批准号:
10532826 - 财政年份:2021
- 资助金额:
$ 38.41万 - 项目类别:
Employing mouse models to translate early detection of pancreas cancer
利用小鼠模型转化胰腺癌的早期检测
- 批准号:
8904197 - 财政年份:2015
- 资助金额:
$ 38.41万 - 项目类别:
Employing mouse models to translate early detection of pancreas cancer
利用小鼠模型转化胰腺癌的早期检测
- 批准号:
9097660 - 财政年份:2015
- 资助金额:
$ 38.41万 - 项目类别:














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