Direct therapeutic intervention of the tumor microenvironment with a potent inhibitor of fibronectin assembly

使用纤连蛋白组装的有效抑制剂对肿瘤微环境进行直接治疗干预

基本信息

  • 批准号:
    10409814
  • 负责人:
  • 金额:
    $ 20.92万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2021
  • 资助国家:
    美国
  • 起止时间:
    2021-06-01 至 2024-05-31
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY Among the hallmarks of cancer, the extracellular matrix contributes to the regulation of each of the hallmark principles underlying tumor progression. Importantly, extracellular matrix stiffness and fiber organization enhance overall breast cancer progression and are associated with poor patient outcome. Biophysical and biochemical cues from fibrillar matrix stiffness have emerged as key regulators of steps in the metastatic cascade, including increased tumor cell invasion, inflammatory signaling, circulating tumor cells, and metastatic outgrowth. Moreover, emerging studies demonstrate that biophysical cues from the ECM impact tumor intrinsic and extrinsic factors implicated in immunotherapy resistance. Taken together, this data suggests that stromal matrix stiffness may be one of the underlying mechanisms driving immunosuppression in the breast tumor microenvironment. Despite the growing evidence that biophysical cues play a key role in disease progression and the mounting interest in therapeutically targeting tumor ECM, there has yet to be an effective therapy directly targeting the stromal matrix in breast cancer. Therefore, we propose to develop a therapeutically useful agent to directly disrupt extracellular matrix assembly, deposition, and organization within the primary and metastatic tumor microenvironments for the clinical treatment of breast cancer. We hypothesize that directly targeting FN assembly with PEGylated-FUD will subsequently reduce tumor fibrosis by inhibiting collagen deposition and fiber alignment resulting in decreased tumor growth and metastatic progression. We further hypothesize that reduced fibronectin and collagen deposition will limit mechanical activation of pro-tumor inflammation resulting in enhanced therapeutic efficacy in combination with immune checkpoint blockade. We will test our hypothesis in the following aims: Aim 1: Determine the efficacy of PEGylated FUD as an anti-cancer therapy in pre-clinical models of breast cancer. Aim 2. Evaluate the impact of PEGylated-FUD on immunosuppressive signaling to enhance anti-PD-L1 therapy for treatment of metastatic disease.
项目总结

项目成果

期刊论文数量(0)
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Glen S. Kwon其他文献

Polymeric micelle nanocarriers in cancer research
Polymeric Micelles for Multi-Drug Delivery in Cancer
  • DOI:
    10.1208/s12249-014-0251-3
  • 发表时间:
    2014-12-11
  • 期刊:
  • 影响因子:
    4.000
  • 作者:
    Hyunah Cho;Tsz Chung Lai;Keishiro Tomoda;Glen S. Kwon
  • 通讯作者:
    Glen S. Kwon
Soluble Self-Assembled Block Copolymers for Drug Delivery
  • DOI:
    10.1023/a:1011991617857
  • 发表时间:
    1999-01-01
  • 期刊:
  • 影响因子:
    4.300
  • 作者:
    Glen S. Kwon;Teruo Okano
  • 通讯作者:
    Teruo Okano
Production of paclitaxel-loaded PEG-emb/em-PLA micelles using PEG for drug loading and freeze-drying
使用聚乙二醇进行药物负载和冷冻干燥来生产紫杉醇负载的聚乙二醇-乳化/包埋-聚乳酸微球
  • DOI:
    10.1016/j.jconrel.2022.08.032
  • 发表时间:
    2022-10-01
  • 期刊:
  • 影响因子:
    11.500
  • 作者:
    Morteza Rasoulianboroujeni;Lauren Repp;Hye Jin Lee;Glen S. Kwon
  • 通讯作者:
    Glen S. Kwon
Paclitaxel Prodrugs with Sustained Release and High Solubility in Poly(ethylene glycol)-b-poly(ε-caprolactone) Micelle Nanocarriers: Pharmacokinetic Disposition, Tolerability, and Cytotoxicity
  • DOI:
    10.1007/s11095-007-9451-9
  • 发表时间:
    2007-10-03
  • 期刊:
  • 影响因子:
    4.300
  • 作者:
    M. Laird Forrest;Jaime A. Yáñez;Connie M. Remsberg;Yusuke Ohgami;Glen S. Kwon;Neal M. Davies
  • 通讯作者:
    Neal M. Davies

Glen S. Kwon的其他文献

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{{ truncateString('Glen S. Kwon', 18)}}的其他基金

Direct therapeutic intervention of the tumor microenvironment with a potent inhibitor of fibronectin assembly
使用纤连蛋白组装的有效抑制剂对肿瘤微环境进行直接治疗干预
  • 批准号:
    10199263
  • 财政年份:
    2021
  • 资助金额:
    $ 20.92万
  • 项目类别:
Oligo(lactic acid)n-Prodrug Nanomedicines for Combination Therapy
用于联合治疗的寡(乳酸)n-前药纳米药物
  • 批准号:
    10371257
  • 财政年份:
    2021
  • 资助金额:
    $ 20.92万
  • 项目类别:
Oligo(lactic acid)n-Prodrug Nanomedicines for Combination Therapy
用于联合治疗的寡聚(乳酸)n-前药纳米药物
  • 批准号:
    10597075
  • 财政年份:
    2021
  • 资助金额:
    $ 20.92万
  • 项目类别:
Co-Delivery of Antifungal Agents: Toxicity and Efficacy in Invasive Candidiasis
抗真菌药物的联合给药:侵袭性念珠菌病的毒性和功效
  • 批准号:
    8497027
  • 财政年份:
    2013
  • 资助金额:
    $ 20.92万
  • 项目类别:
Co-Delivery of Antifungal Agents: Toxicity and Efficacy in Invasive Candidiasis
抗真菌药物的联合给药:侵袭性念珠菌病的毒性和功效
  • 批准号:
    8786047
  • 财政年份:
    2013
  • 资助金额:
    $ 20.92万
  • 项目类别:
Co-Delivery of Antifungal Agents: Toxicity and Efficacy in Invasive Candidiasis
抗真菌药物的联合给药:侵袭性念珠菌病的毒性和功效
  • 批准号:
    8605161
  • 财政年份:
    2013
  • 资助金额:
    $ 20.92万
  • 项目类别:
Tri-modal Polymeric Micelles for 'See & Treat' Applications in Surgical Oncology
用于“See”的三峰聚合物胶束
  • 批准号:
    8298518
  • 财政年份:
    2011
  • 资助金额:
    $ 20.92万
  • 项目类别:
Tri-modal Polymeric Micelles for 'See & Treat' Applications in Surgical Oncology
用于“See”的三峰聚合物胶束
  • 批准号:
    8175145
  • 财政年份:
    2011
  • 资助金额:
    $ 20.92万
  • 项目类别:
BIOSPECIFIC POLYMER ENZYME CONJUGATES FOR DRUG DELIVERY
用于药物输送的生物特异性聚合物酶缀合物
  • 批准号:
    6262537
  • 财政年份:
    2001
  • 资助金额:
    $ 20.92万
  • 项目类别:
BIOSPECIFIC POLYMER ENZYME CONJUGATES FOR DRUG DELIVERY
用于药物输送的生物特异性聚合物酶缀合物
  • 批准号:
    6489389
  • 财政年份:
    2001
  • 资助金额:
    $ 20.92万
  • 项目类别:

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以额叶功能为中心的汽车驾驶能力评价方法的建立及其在事故预测中的应用
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