NEXT GENERATION APPROACHES TO BREAST CANCER USING IMAGE GUIDED DRUG DELIVERY

使用图像引导药物输送的下一代乳腺癌治疗方法

基本信息

  • 批准号:
    8450023
  • 负责人:
  • 金额:
    $ 45.57万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2011
  • 资助国家:
    美国
  • 起止时间:
    2011-07-01 至 2016-04-30
  • 项目状态:
    已结题

项目摘要

Angiogenesis is a critical feature of malignant tumor growth and metastasis and anti-angiogenesis targeting has improved survival in numerous solid tumor malignancies. However, anti-angiogenesis therapy cannot be expected to be equally effective across tumor types, sizes, locations, stages and grades. The utility of antiangiogenesis treatment with bevacizumab in breast cancer has been hotly debated in the press and scientific forums based on recent clinical trial data, however, current clinical recommendations affirm bevacizumab as an appropriate therapeutic option in combination with paclitaxel for metastatic breast cancer. In this proposal, we hypothesize that the identification of breast cancers with active neoangiogenesis will enhance the efficacy of targeted antiangiogenesis therapy. We contend that a compelling clinical need exists for quantitative molecular imaging to identify and follow breast cancer patients likely to respond to anti-angiogenic treatment. Although anti-VEGF monoclonal and receptor tyrosine kinase inhibitor drugs are approved in the clinic as antiangiogenic treatments, costing >$100,000/patient and exhibiting well documented adverse effects, alternative theranostic nanomedicine approaches specifically targeting neovessel endothelium with minute doses of highly potent, compounds, such as fumagillin, may represent an improved approach. We hypothesize that the efficacy of theranostic nanoparticles targeted to neovessel endothelium will reflect tumor dependence on angiogenesis for progression. We further hypothesize that the benefits of theranostic antiangiogenic nanoparticles can be enhanced using non-cross resistant anti-angiogeneic compounds,such as amino-bisphosphonates that have direct and indirect cytotoxic effects on neoangiogenesis and tumor-recruited myeloid cells that secrete pro-angiogeneic factors. Osteoprotegerin (OPG) receptor activator of nuclear factor-kB (RANK) and RANK ligand (RANKL) pathway plays a central role in bone destruction through osteoclast differentiation and osteolysis due to bone metastasis, which occurs in 70% of women with breast cancer. While amino-bisphosphonates (N-BP) and RANKL-Ab disrupt the OPG-RANK-RANKL system, inhibiting osteoclast formation or function, they can also induce apoptosis and antiangiogenesis in some cancers, including breast. We hypothesize that acute nanomedicine-based antiangiogenic therapy combined with N-BP treatment would be effective as pre-adjuvant and maintenance therapy. The specific aims of this study are: Aim 1. Compare the effectiveness of anti-angiogenesis and tumor progression with bevacizumab versus ¿v¿3- fumagillin-prodrug nanoparticles in soft tissue, visceral, and metastases and correlate treatment response with pretreatment tumor size and neovasculature character. Aim 2. Determine the efficacy of N-BP in combination with theranostic nanoparticles targeted to neovessel endothelium on breast cancer tumor growth, metastasis and survival.
血管生成是恶性肿瘤生长转移和抗血管生成靶向的重要特征

项目成果

期刊论文数量(0)
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Gregory M Lanza其他文献

Quantitative molecular imaging of angiogenesis-targeted fluorinated nanoparticles: new approaches for B<sub>1</sub>-mapping compensation for <sup>19</sup>F-MRI
  • DOI:
    10.1186/1532-429x-15-s1-o83
  • 发表时间:
    2013-01-30
  • 期刊:
  • 影响因子:
  • 作者:
    Matthew J Goette;Anne H Schmieder;Todd A Williams;John S Allen;Jochen Keupp;Gregory M Lanza;Samuel A Wickline;Shelton D Caruthers
  • 通讯作者:
    Shelton D Caruthers
1054-155 Antiangiogenic therapy of early atherosclerosis with paramagnetic <em>α</em><sub><em>ν</em></sub><em>β</em><sub>3</sub>-integrin-targeted fumagillin nanoparticles
  • DOI:
    10.1016/s0735-1097(04)91363-0
  • 发表时间:
    2004-03-03
  • 期刊:
  • 影响因子:
  • 作者:
    Patrick M Winter;Anne M Morawski;Shelton D Caruthers;Thomas D Harris;Ralph W Fuhrhop;Huiying Zhang;John S Allen;Elizabeth K Lacy;Todd A Williams;Samuel A Wickline;Gregory M Lanza
  • 通讯作者:
    Gregory M Lanza
110 Myofiber developmental plasticity in fetal hearts delineated with diffusion tensor MRI
  • DOI:
    10.1186/1532-429x-10-s1-a11
  • 发表时间:
    2008-10-22
  • 期刊:
  • 影响因子:
  • 作者:
    Lei Zhang;Junjie Chen;Allyson Gibson;Mark R Holland;Gregory M Lanza;Samuel A Wickline
  • 通讯作者:
    Samuel A Wickline

Gregory M Lanza的其他文献

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{{ truncateString('Gregory M Lanza', 18)}}的其他基金

OVERCOMING THE PROTECTIVE BARRIERS OF BREAST CANCER IN BONE MARROW WITH TARGETED PRODRUG NANOTHERAPY
通过靶向前药纳米疗法克服骨髓中乳腺癌的保护性屏障
  • 批准号:
    10320444
  • 财政年份:
    2018
  • 资助金额:
    $ 45.57万
  • 项目类别:
Targeted Nanoparticles of Bismuth Organo Complexes for Spectral CT Imaging of Cor
用于 Cor 光谱 CT 成像的铋有机配合物靶向纳米颗粒
  • 批准号:
    8253172
  • 财政年份:
    2012
  • 资助金额:
    $ 45.57万
  • 项目类别:
Targeted Nanoparticles of Bismuth Organo Complexes for Spectral CT Imaging of Cor
用于 Cor 光谱 CT 成像的铋有机复合物靶向纳米颗粒
  • 批准号:
    8712764
  • 财政年份:
    2012
  • 资助金额:
    $ 45.57万
  • 项目类别:
Theranostic Approach to Asthma Using Anti-Angiogenic Nanomedicine
使用抗血管生成纳米药物治疗哮喘的方法
  • 批准号:
    9031128
  • 财政年份:
    2012
  • 资助金额:
    $ 45.57万
  • 项目类别:
Theranostic Approach to Asthma Using Anti-Angiogenic Nanomedicine
使用抗血管生成纳米药物治疗哮喘的方法
  • 批准号:
    8456169
  • 财政年份:
    2012
  • 资助金额:
    $ 45.57万
  • 项目类别:
Targeted Nanoparticles of Bismuth Organo Complexes for Spectral CT Imaging of Cor
用于 Cor 光谱 CT 成像的铋有机配合物靶向纳米颗粒
  • 批准号:
    8497716
  • 财政年份:
    2012
  • 资助金额:
    $ 45.57万
  • 项目类别:
Theranostic Approach to Asthma Using Anti-Angiogenic Nanomedicine
使用抗血管生成纳米药物治疗哮喘的方法
  • 批准号:
    8274016
  • 财政年份:
    2012
  • 资助金额:
    $ 45.57万
  • 项目类别:
Theranostic Approach to Asthma Using Anti-Angiogenic Nanomedicine
使用抗血管生成纳米药物治疗哮喘的方法
  • 批准号:
    8618918
  • 财政年份:
    2012
  • 资助金额:
    $ 45.57万
  • 项目类别:
NEXT GENERATION APPROACHES TO BREAST CANCER USING IMAGE GUIDED DRUG DELIVERY
使用图像引导药物输送的下一代乳腺癌治疗方法
  • 批准号:
    8848042
  • 财政年份:
    2011
  • 资助金额:
    $ 45.57万
  • 项目类别:
NEXT GENERATION APPROACHES TO BREAST CANCER USING IMAGE GUIDED DRUG DELIVERY
使用图像引导药物输送的下一代乳腺癌治疗方法
  • 批准号:
    8186086
  • 财政年份:
    2011
  • 资助金额:
    $ 45.57万
  • 项目类别:

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