Screening for DNA damage response modulators in glioblastoma stem cells

胶质母细胞瘤干细胞中 DNA 损伤反应调节剂的筛选

基本信息

  • 批准号:
    10038588
  • 负责人:
  • 金额:
    $ 42万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2020
  • 资助国家:
    美国
  • 起止时间:
    2020-09-15 至 2022-07-31
  • 项目状态:
    已结题

项目摘要

Abstract There is presently no cure for high grade gliomas which are associated with a bleak prognosis and a poor quality of life. GBM patients typically undergo surgical resection followed by radiation therapy (RT) combined with the alkylating agent temozolomide (TMZ). However, virtually all GBM patients either fail to respond to this treatment, or ultimately develop resistance, underlining the urgency for effective adjuvant therapies. Both RT and TMZ can target tumor cells by causing lethal DNA double-strand breaks, which could be recognized and repaired by the intrinsic DNA damage response (DDR) thus protecting against DNA damage-induced cell death. Further, GBMs are enriched in a subset population of glioma cancer stem cells (GSCs), characterized by an upregulated DDR which contributes to their superior therapeutic resistance. Targeting DNA repair can increase/restore sensitivity of brain tumors to TMZ and RT, thus increasing therapeutic efficacy and minimizing tumor recurrence. We have designed a rapid, versatile and highly sensitive reporter that can detect and quantify minute amounts of DNA double-strand break repairs such as homology-directed repair as well as non-homologous end joining without disrupting cells. Here we propose to use this reporter in order to identify modulators of DNA damage repair in GSCs. In Aim 1 (R61 phase), we will develop and optimize a high-throughput screening assay to monitor DDR in GSCs. In Aim 2 (R33 phase), we will use this assay to screen for compounds which inhibit DNA damage repair. Upon completion of this project, this screen should identify novel compounds which effectively sensitize GSCs to chemoradiotherapy and increase the efficacy of genotoxic therapeutics.
摘要

项目成果

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Christian Elias Badr其他文献

Christian Elias Badr的其他文献

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{{ truncateString('Christian Elias Badr', 18)}}的其他基金

Translocon-regulated ER proteostasis in glioblastoma
胶质母细胞瘤中易位蛋白调节的内质网蛋白稳态
  • 批准号:
    10301296
  • 财政年份:
    2021
  • 资助金额:
    $ 42万
  • 项目类别:
Role of ER Stress and Fatty Acid Metabolism in Glioma Stem Cells
内质网应激和脂肪酸代谢在胶质瘤干细胞中的作用
  • 批准号:
    10665639
  • 财政年份:
    2020
  • 资助金额:
    $ 42万
  • 项目类别:
Role of ER stress and fatty acid metabolism in glioma stem cells
内质网应激和脂肪酸代谢在胶质瘤干细胞中的作用
  • 批准号:
    10261413
  • 财政年份:
    2020
  • 资助金额:
    $ 42万
  • 项目类别:
Role of ER stress and fatty acid metabolism in glioma stem cells
内质网应激和脂肪酸代谢在胶质瘤干细胞中的作用
  • 批准号:
    10461146
  • 财政年份:
    2020
  • 资助金额:
    $ 42万
  • 项目类别:
Screening for DNA Damage Response Modulators in Glioblastoma Stem Cells
胶质母细胞瘤干细胞中 DNA 损伤反应调节剂的筛选
  • 批准号:
    10683338
  • 财政年份:
    2020
  • 资助金额:
    $ 42万
  • 项目类别:
Screening for DNA damage response modulators in glioblastoma stem cells
胶质母细胞瘤干细胞中 DNA 损伤反应调节剂的筛选
  • 批准号:
    10618739
  • 财政年份:
    2020
  • 资助金额:
    $ 42万
  • 项目类别:
Identifying vulnerabilities and therapeutic targets in Glioma Stem Cells
识别神经胶质瘤干细胞的脆弱性和治疗靶点
  • 批准号:
    8948656
  • 财政年份:
    2015
  • 资助金额:
    $ 42万
  • 项目类别:

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