Normalizing PDAC stroma with PCBP2 siRNA nanoparticles to improve the antitumor activity of chemotherapy and immunotherapy
使用 PCBP2 siRNA 纳米颗粒使 PDAC 基质正常化以提高化疗和免疫治疗的抗肿瘤活性
基本信息
- 批准号:10606872
- 负责人:
- 金额:$ 36.86万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-04-01 至 2028-03-31
- 项目状态:未结题
- 来源:
- 关键词:AffinityAnimalsApoptoticBindingBinding ProteinsBiodistributionBiological AssayCancer EtiologyCellsCharacteristicsCholesterolClinical TrialsCollagen Type ICombined Modality TherapyDepositionDesmoplasticDrug KineticsExhibitsExtracellular MatrixFibroblastsFunctional disorderGenesGenetic TranscriptionGoalsHepatic Stellate CellHumanImmune EvasionImmunotherapyImplantIn VitroIntegrinsIntercellular FluidLinkMorphologyMusMyofibroblastNIH 3T3 CellsNeoplasm MetastasisNude MicePD-1/PD-L1Pancreatic Ductal AdenocarcinomaPatientsPenetrationPeptidesPharmaceutical PreparationsPhenotypePlayProductionProliferatingProteinsRoleSafetySerumSmall Interfering RNASolidSolubilitySpecificityStressStructure-Activity RelationshipSurvival RateTherapeutic IndexTissuesToxicologyVertebral columnX-Ray CrystallographyXenograft procedureangiogenesisanti-PD-L1cell transformationchemotherapycrosslinkeffector T cellgemcitabineimprovedin vitro activityin vivomigrationmortalitymouse modelnanoparticleneoplastic cellnovelpancreatic ductal adenocarcinoma cellpancreatic stellate cellplectinpressureprogrammed cell death ligand 1restrainttumortumor growthtumorigenesisuptake
项目摘要
Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer-related
mortality in the world. Desmoplasia is the most prominent characteristic of PDAC and comprises
up to 80% of the tumor mass. Desmoplasia plays important roles in tumorigenesis and
aggressiveness by promoting the proliferation and metastasis of tumor cells, enhancing
angiogenesis, impeding drug penetration, and contributing to immune evasion. However, clinical
trials employing strategies to deplete PDAC stroma have failed. The stroma acts not only as a
barrier to the penetration of drug and effector T cells, but also as a barrier to restrain the
metastasis of PDAC tumors. Complete depletion of the stroma, therefore, leads to a more
aggressive tumor and a poor survival rate. By contrast, normalization, instead of depletion, of the
stroma in combination with chemotherapy or immunotherapy to kill tumor cells within the stromal
microenvironment is a promising strategy for PDAC therapy.
In the stromal microenvironment, activated pancreatic stellate cells (PSCs) transform from a
quiescent state into a myofibroblast-like phenotype and express a large amount of extracellular
matrix (ECM). Type I collagen proteins are the main component of the ECM and are responsible
for the major desmoplastic reaction. High levels of type I collagen are associated with a low
survival rate for patients with PDAC. Type I collagen promotes the proliferation and migration of
PDAC cells and inhibits apoptotic cells by binding to integrin.
We discovered that silencing the poly(rC)-binding protein 2 (CP2) with siRNA reverses the
accumulation of type I collagen in activated PSCs. Our central hypothesis is that silencing CP2
modulates the PDAC stroma, thus improving the therapeutic index of chemotherapy and
immunotherapy. The long-term goal of the project is to develop a combination therapy strategy to
treat PDAC.
胰腺导管腺癌(Pancreatic ductal adencarcinoma, PDAC)是引起肿瘤相关疾病的主要原因之一
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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Kun Cheng其他文献
Kun Cheng的其他文献
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{{ truncateString('Kun Cheng', 18)}}的其他基金
Development of a targeted delivery platform for checkpoint inhibitors
检查点抑制剂靶向递送平台的开发
- 批准号:
9980337 - 财政年份:2018
- 资助金额:
$ 36.86万 - 项目类别:
Development of a targeted delivery platform for checkpoint inhibitors
检查点抑制剂靶向递送平台的开发
- 批准号:
10468185 - 财政年份:2018
- 资助金额:
$ 36.86万 - 项目类别:
Development of a targeted delivery platform for checkpoint inhibitors
检查点抑制剂靶向递送平台的开发
- 批准号:
9756345 - 财政年份:2018
- 资助金额:
$ 36.86万 - 项目类别:
Development of a targeted delivery platform for checkpoint inhibitors
检查点抑制剂靶向递送平台的开发
- 批准号:
10250482 - 财政年份:2018
- 资助金额:
$ 36.86万 - 项目类别:
Peptide-based conjugate for a water-insoluble drug treating advanced prostate cancer
用于治疗晚期前列腺癌的水不溶性药物的肽缀合物
- 批准号:
10176872 - 财政年份:2017
- 资助金额:
$ 36.86万 - 项目类别:
Peptide-based conjugate for a water-insoluble drug treating advanced prostate cancer
用于治疗晚期前列腺癌的水不溶性药物的肽缀合物
- 批准号:
9383987 - 财政年份:2017
- 资助金额:
$ 36.86万 - 项目类别:
Peptide-based conjugate for a water-insoluble drug treating advanced prostate cancer
用于治疗晚期前列腺癌的水不溶性药物的肽缀合物
- 批准号:
9975195 - 财政年份:2017
- 资助金额:
$ 36.86万 - 项目类别:
Combination therapy using siRNA nanocompelex and PD-L1 inhibitor for alcoholic liver fibrosis
siRNA纳米复合物与PD-L1抑制剂联合治疗酒精性肝纤维化
- 批准号:
10217954 - 财政年份:2012
- 资助金额:
$ 36.86万 - 项目类别:
Combination therapy using siRNA nanocompelex and PD-L1 inhibitor for alcoholic liver fibrosis
siRNA纳米复合物与PD-L1抑制剂联合治疗酒精性肝纤维化
- 批准号:
9980233 - 财政年份:2012
- 资助金额:
$ 36.86万 - 项目类别:
Targeted delivery of PCBP2 siRNA for treating alcoholic liver fibrosis
PCBP2 siRNA 的靶向递送治疗酒精性肝纤维化
- 批准号:
8910579 - 财政年份:2012
- 资助金额:
$ 36.86万 - 项目类别:
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