Project 3: The Role of Macrophages in Resistance to Anti-VEGF Drugs in Ovarian Cancer

项目3:巨噬细胞在卵巢癌抗VEGF药物耐药中的作用

基本信息

  • 批准号:
    10251116
  • 负责人:
  • 金额:
    $ 34.45万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2017
  • 资助国家:
    美国
  • 起止时间:
    2017-09-22 至 2023-08-31
  • 项目状态:
    已结题

项目摘要

Project 3 SUMMARY/ABSTRACT Angiogenesis is known to play a critical role in cancer growth and metastasis. Among the many potential targets, vascular endothelial growth factor (VEGF) has been well recognized to play an important role in angiogenesis, and drugs targeting this pathway have been used against ovarian and other cancers. Clinical use of anti-VEGF therapy, however, has yielded only modest improvement in progression-free or overall survival of patients with ovarian cancer, likely due to adaptive changes in the tumor microenvironment. There remains an unmet need to develop methods to enhance efficacy of anti-VEGF therapy and block growth- promoting adaptive changes. The mechanisms of adaptive resistance to anti-VEGF treatment are largely unknown. Understanding the adaptive resistance to anti-VEGF treatment has the potential to significantly enhance the efficacy of anti-VEGF therapy in ovarian cancer patients. Our preliminary findings suggest that tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs) are substantially increased in the anti-VEGF therapy-resistant tumors and TAM depletion (with CSF1R inhibitor) can improve the effectiveness of anti-VEGF therapy; however, the mechanisms by which this occurs are not well understood. In this proposal, we will explore the mechanisms by which macrophages contribute to adaptive resistance to anti-VEGF treatment and test the efficacy of dual targeting of VEGF and TAMs/MDSCs. Our central hypothesis is that targeting TAMs in the microenvironment will reverse the immunophenotypical alterations induced by bevacizumab and improve clinical efficacy. We will conduct a novel, induction, randomized supplementation clinical study to assess the impact of adding a CSF1R inhibitor to identify and overcome these effects as measured by objective response and event-free survival. The proposed work is highly translational and has the potential to significantly enhance the efficacy of anti-VEGF therapy in ovarian cancer patients.
项目3摘要/摘要

项目成果

期刊论文数量(0)
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会议论文数量(0)
专利数量(0)

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ANIL K SOOD其他文献

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{{ truncateString('ANIL K SOOD', 18)}}的其他基金

Administrative Core
行政核心
  • 批准号:
    10709228
  • 财政年份:
    2023
  • 资助金额:
    $ 34.45万
  • 项目类别:
Targeting EGFL6 in Ovarian Cancer
靶向 EGFL6 治疗卵巢癌
  • 批准号:
    10709231
  • 财政年份:
    2023
  • 资助金额:
    $ 34.45万
  • 项目类别:
Harnessing the power of exosomes for non-coding RNA delivery
利用外泌体的力量进行非编码 RNA 递送
  • 批准号:
    9754614
  • 财政年份:
    2017
  • 资助金额:
    $ 34.45万
  • 项目类别:
Harnessing the power of exosomes for non-coding RNA delivery
利用外泌体的力量进行非编码 RNA 递送
  • 批准号:
    9979631
  • 财政年份:
    2017
  • 资助金额:
    $ 34.45万
  • 项目类别:
Developmental Research Program
发展研究计划
  • 批准号:
    10251119
  • 财政年份:
    2017
  • 资助金额:
    $ 34.45万
  • 项目类别:
Harnessing the power of exosomes for non-coding RNA delivery
利用外泌体的力量进行非编码 RNA 递送
  • 批准号:
    9388779
  • 财政年份:
    2017
  • 资助金额:
    $ 34.45万
  • 项目类别:
Harnessing the power of exosomes for non-coding RNA delivery
利用外泌体的力量进行非编码 RNA 递送
  • 批准号:
    10670211
  • 财政年份:
    2017
  • 资助金额:
    $ 34.45万
  • 项目类别:
Project 3: The Role of Macrophages in Resistance to Anti-VEGF Drugs in Ovarian Cancer
项目3:巨噬细胞在卵巢癌抗VEGF药物耐药中的作用
  • 批准号:
    10005297
  • 财政年份:
    2017
  • 资助金额:
    $ 34.45万
  • 项目类别:
Career Enhancement Program
职业提升计划
  • 批准号:
    10005302
  • 财政年份:
    2017
  • 资助金额:
    $ 34.45万
  • 项目类别:
Career Enhancement Program
职业提升计划
  • 批准号:
    10251120
  • 财政年份:
    2017
  • 资助金额:
    $ 34.45万
  • 项目类别:

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