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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：
RAGHU KALLURI
金额：
$ 38.41万
依托单位：
UNIVERSITY OF TX MD ANDERSON CAN CTR
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：
https://reporter.nih.gov/project-details/9230198
关键词：
Apoptosis Applications Grants Biological Assay Biology Blood Circulation Brain CD47 gene Cell Proliferation Cells Clinic Clinical Codon Nucleotides Complement Coupled Cultured Cells DNA Data Disease Eating Electroporation Endopeptidase K Engineering Exhibits Extracellular Protein Fibroblasts Frequencies Future Genetic Genetic study Genetically Engineered Mouse Glycine Half-Life Human ITGAM gene Image Impairment Integrins Investigation KRAS2 gene Label Liposomes Liver Lung Malignant Neoplasms Malignant neoplasm of pancreas Mediating Mediator of activation protein Molecular Mus Mutation Oncogenic Pancreas Pancreatic Ductal Adenocarcinoma Pathogenesis Pathway interactions Patients Performance Phagocytes Pharmaceutical Preparations Pharmacology Physiological Play Process Proteins Proteomics RNA RNA Interference Research Role Route Signal Transduction Small Interfering RNA Survival Rate System Techniques Tertiary Protein Structure Testing Therapeutic Tissues Trypsin Western Blotting Xenograft procedure base cancer therapy design dosage effective therapy exosome experimental study extracellular vesicles imaging modality improved insight knowledge translation macrophage monocyte mouse model nanoparticle neutralizing antibody novel strategies novel therapeutics outcome forecast pancreatic cancer cells pancreatic neoplasm penis foreskin pre-clinical preclinical study programs small hairpin RNA standard of care therapeutic evaluation tumor tumor 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