Targeted therapies to correct genomic instability in Brca1-deficient cells.

纠正 Brca1 缺陷细胞基因组不稳定性的靶向治疗。

基本信息

  • 批准号:
    8725080
  • 负责人:
  • 金额:
    $ 24.15万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2012
  • 资助国家:
    美国
  • 起止时间:
    2012-09-20 至 2015-08-31
  • 项目状态:
    已结题

项目摘要

Project Abstract: Targeted therapies to correct genomic instability in BRCA1-deficient cells. Individuals with mutations in either the BRCA1 or BRCA2 gene account for approximately 5- 10% of all breast cancers in the developed world. For women carrying a mutant BRCA1 gene, there is a nearly 80% lifetime chance of developing breast cancer and a nearly 40% chance of developing ovarian cancer. At present, there are no effective or targeted molecular therapies that modify this susceptibility. In the absence of BRCA1 activity, cells are incapable of repairing DNA breaks through the homologous recombination pathway (HR). HR provides an error free mechanism to repair DNA damage, but in the absence of efficient HR, cells can repair DNA damage though other error-prone pathways. The use of these pathways can lead to the formation of abnormal and potentially harmful chromosomal structures that promote tumorigenesis. Indeed, it is generally believed that the inability of BRCA1 deficient cells to perform HR is central to its role in tumor formation. Recent reports have demonstrated that it is possible to restore HR activity in BRCA1 deficient cells by deletion of the gene for the DNA damage response factor, 53BP1. These results suggest that in BRCA1-deficient cells, 53BP1 may act as a molecular inhibitor of HR. Furthermore, inhibiting 53BP1 activity may reduce the incidence of BRCA1-mediated breast cancer. The proposed research will explore the novel notion that it may be possible to restore near normal HR activity in BRCA1 cells and tissues. The interplay between 53BP1 and BRCA1 will be further characterized to refine our understanding of the underlying mechanism, as well as an attempt to develop lead compounds that inhibit 53BP1 function. A fuller understanding of this phenomenon will lead to targeted therapies to reduce the lifetime risk of tumor formation in BRCA1 and potentially BRCA2 carriers.
项目摘要: 靶向治疗以纠正BRCA 1缺陷细胞中的基因组不稳定性。 BRCA 1或BRCA 2基因突变的个体约占5- 占发达国家乳腺癌的10%。对于携带突变BRCA 1基因的女性, 一生中有近80%的机会患乳腺癌, 患上卵巢癌目前尚无有效的或靶向的分子治疗方法 改变了这种易感性。在缺乏BRCA 1活性的情况下,细胞无法修复 DNA通过同源重组途径(HR)突破。HR提供无错误 修复DNA损伤的机制,但在缺乏有效的HR的情况下,细胞可以修复DNA 通过其他容易出错的路径损坏。使用这些途径可以导致 形成异常和潜在有害的染色体结构, 肿瘤发生事实上,人们普遍认为BRCA 1缺陷细胞无法 执行HR是其在肿瘤形成中的作用的核心。最近的报告表明, 可能通过删除DNA的基因来恢复BRCA 1缺陷细胞中的HR活性 损伤响应因子53 BP 1。这些结果表明,在BRCA 1缺陷细胞中,53 BP 1 可能作为HR的分子抑制剂。此外,抑制53 BP 1活性可能会降低 BRCA 1介导的乳腺癌的发病率。这项拟议中的研究将探讨小说 这意味着有可能在BRCA 1细胞和组织中恢复接近正常的HR活性。 53 BP 1和BRCA 1之间的相互作用将进一步表征,以完善我们的 了解潜在的机制,以及尝试开发先导化合物 抑制53 BP 1功能。对这一现象的更充分理解将导致有针对性的 降低BRCA 1和潜在BRCA 2中肿瘤形成的终生风险的疗法 载波

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)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Samuel Bunting其他文献

Samuel Bunting的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Samuel Bunting', 18)}}的其他基金

Project 1: Recruitment of the BRCA1-associated Homologous Recombination Machinery
项目1:BRCA1相关同源重组机制的招募
  • 批准号:
    10599897
  • 财政年份:
    2021
  • 资助金额:
    $ 24.15万
  • 项目类别:
Project 1: Recruitment of the BRCA1-associated Homologous Recombination Machinery
项目1:BRCA1相关同源重组机制的招募
  • 批准号:
    10396607
  • 财政年份:
    2021
  • 资助金额:
    $ 24.15万
  • 项目类别:
Control of commitment steps in mammalian homologous recombination
哺乳动物同源重组中承诺步骤的控制
  • 批准号:
    9762020
  • 财政年份:
    2015
  • 资助金额:
    $ 24.15万
  • 项目类别:
Control of commitment steps in mammalian homologous recombination
哺乳动物同源重组中承诺步骤的控制
  • 批准号:
    9052744
  • 财政年份:
    2015
  • 资助金额:
    $ 24.15万
  • 项目类别:
Targeted therapies to correct genomic instability in Brca1-deficient cells.
纠正 Brca1 缺陷细胞基因组不稳定性的靶向治疗。
  • 批准号:
    8528236
  • 财政年份:
    2012
  • 资助金额:
    $ 24.15万
  • 项目类别:
Targeted therapies to correct genomic instability in Brca1-deficient cells.
纠正 Brca1 缺陷细胞基因组不稳定性的靶向治疗。
  • 批准号:
    8548299
  • 财政年份:
    2012
  • 资助金额:
    $ 24.15万
  • 项目类别:

相似海外基金

How Does Particle Material Properties Insoluble and Partially Soluble Affect Sensory Perception Of Fat based Products
不溶性和部分可溶的颗粒材料特性如何影响脂肪基产品的感官知觉
  • 批准号:
    BB/Z514391/1
  • 财政年份:
    2024
  • 资助金额:
    $ 24.15万
  • 项目类别:
    Training Grant
BRC-BIO: Establishing Astrangia poculata as a study system to understand how multi-partner symbiotic interactions affect pathogen response in cnidarians
BRC-BIO:建立 Astrangia poculata 作为研究系统,以了解多伙伴共生相互作用如何影响刺胞动物的病原体反应
  • 批准号:
    2312555
  • 财政年份:
    2024
  • 资助金额:
    $ 24.15万
  • 项目类别:
    Standard Grant
RII Track-4:NSF: From the Ground Up to the Air Above Coastal Dunes: How Groundwater and Evaporation Affect the Mechanism of Wind Erosion
RII Track-4:NSF:从地面到沿海沙丘上方的空气:地下水和蒸发如何影响风蚀机制
  • 批准号:
    2327346
  • 财政年份:
    2024
  • 资助金额:
    $ 24.15万
  • 项目类别:
    Standard Grant
Graduating in Austerity: Do Welfare Cuts Affect the Career Path of University Students?
紧缩毕业:福利削减会影响大学生的职业道路吗?
  • 批准号:
    ES/Z502595/1
  • 财政年份:
    2024
  • 资助金额:
    $ 24.15万
  • 项目类别:
    Fellowship
Insecure lives and the policy disconnect: How multiple insecurities affect Levelling Up and what joined-up policy can do to help
不安全的生活和政策脱节:多种不安全因素如何影响升级以及联合政策可以提供哪些帮助
  • 批准号:
    ES/Z000149/1
  • 财政年份:
    2024
  • 资助金额:
    $ 24.15万
  • 项目类别:
    Research Grant
感性個人差指標 Affect-X の構築とビスポークAIサービスの基盤確立
建立个人敏感度指数 Affect-X 并为定制人工智能服务奠定基础
  • 批准号:
    23K24936
  • 财政年份:
    2024
  • 资助金额:
    $ 24.15万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
How does metal binding affect the function of proteins targeted by a devastating pathogen of cereal crops?
金属结合如何影响谷类作物毁灭性病原体靶向的蛋白质的功能?
  • 批准号:
    2901648
  • 财政年份:
    2024
  • 资助金额:
    $ 24.15万
  • 项目类别:
    Studentship
Investigating how double-negative T cells affect anti-leukemic and GvHD-inducing activities of conventional T cells
研究双阴性 T 细胞如何影响传统 T 细胞的抗白血病和 GvHD 诱导活性
  • 批准号:
    488039
  • 财政年份:
    2023
  • 资助金额:
    $ 24.15万
  • 项目类别:
    Operating Grants
New Tendencies of French Film Theory: Representation, Body, Affect
法国电影理论新动向:再现、身体、情感
  • 批准号:
    23K00129
  • 财政年份:
    2023
  • 资助金额:
    $ 24.15万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
The Protruding Void: Mystical Affect in Samuel Beckett's Prose
突出的虚空:塞缪尔·贝克特散文中的神秘影响
  • 批准号:
    2883985
  • 财政年份:
    2023
  • 资助金额:
    $ 24.15万
  • 项目类别:
    Studentship
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了