Bidirectional interaction of platelets and tumor cells in patients with glioblastoma

胶质母细胞瘤患者血小板与肿瘤细胞的双向相互作用

基本信息

  • 批准号:
    10684771
  • 负责人:
  • 金额:
    $ 56.05万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2018
  • 资助国家:
    美国
  • 起止时间:
    2018-12-05 至 2024-08-31
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY Glioblastoma is among the most lethal of all cancers and the most common primary malignant brain tumor, typically lethal by 15 months. After initial tumor resection, we rely on an imperfect measure of disease response, namely magnetic resonance brain imaging, as obtaining tumor tissue at recurrence is often dangerous or fails to impact survival and is rarely performed. Indeed, many patients rely only on a tiny biopsy for initial diagnosis with no ability for subsequent deep molecular analyses, let alone monitoring of disease over time. The current proposal will address a fundamental gap in the field of GBM, i.e. the lack of predictors not dependent on the availability of tumor tissue and those that can provide real-time, tissue-free tumor monitoring, which is particularly critical in monitoring treatment response and assessing disease progression longitudinally. Blood-based biomarkers such as circulating tumor cells and cell free DNA are attractive, but have yet to provide meaningful results in GBM (compared to other cancers) and have yet to become clinical diagnostics. Tumor educated platelets (TEPs) has recently been reported and shown to contain tumor-specific gene expression signatures that are associated with outcome for several tumor types, but the clinical value and the mechanisms of enrichment of TEPs are unknown. The overall goals of this proposal are to elucidate the mechanism underlying the tumor cell–platelet interaction that leads to TEPs and to develop a TEP-based liquid biopsy platform for longitudinal monitoring of disease in patients with GBM. In this project, we will test the hypothesis that platelet numbers are increased in response to tumor signaling in the bone marrow and that platelets take up tumor- derived extracellular vesicles containing RNA cargo in a PDPN dependent manner. TEP RNA signatures reflect underlying tumor biology, growth, and treatment resistance, and will be utilized as biomarkers. In Aim 1, we will test the hypothesis that pro-inflammatory cytokine-mediated paraneoplastic thrombocytosis promotes formation of TEP signatures in GBM. In Aim 2, we will test the hypothesis that PDPN interaction with the CLEC2 receptor contributes to transfer of RNA from tumor cells to platelets. In Aim 3, we will test the hypothesis that TEP RNA signatures can be used to monitor disease burden longitudinally in patients with GBM.
项目总结

项目成果

期刊论文数量(1)
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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KRISHNA PL BHAT其他文献

KRISHNA PL BHAT的其他文献

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{{ truncateString('KRISHNA PL BHAT', 18)}}的其他基金

Novel Roles of TAZ and YAP in DNA Damage Repair with 3D Genome Organization and the Therapeutic Resistance in Glioblastoma
TAZ 和 YAP 在 3D 基因组组织 DNA 损伤修复中的新作用以及胶质母细胞瘤的治疗耐药性
  • 批准号:
    10649830
  • 财政年份:
    2023
  • 资助金额:
    $ 56.05万
  • 项目类别:
Exploiting cell fate transition to overcome radiation resistance in glioblastoma
利用细胞命运转变克服胶质母细胞瘤的辐射抗性
  • 批准号:
    10719050
  • 财政年份:
    2023
  • 资助金额:
    $ 56.05万
  • 项目类别:
Developing a NF-κB/GADD45b targeting strategy for glioblastoma
制定胶质母细胞瘤的 NF-κB/GADD45b 靶向策略
  • 批准号:
    9901485
  • 财政年份:
    2019
  • 资助金额:
    $ 56.05万
  • 项目类别:
Bidirectional interaction of platelets and tumor cells in patients with glioblastoma
胶质母细胞瘤患者血小板和肿瘤细胞的双向相互作用
  • 批准号:
    10468836
  • 财政年份:
    2018
  • 资助金额:
    $ 56.05万
  • 项目类别:

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