A novel set of molecular markers to measure metastatic neuroblastoma

一套用于测量转移性神经母细胞瘤的新型分子标记物

基本信息

  • 批准号:
    7268042
  • 负责人:
  • 金额:
    $ 13.3万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2006
  • 资助国家:
    美国
  • 起止时间:
    2006-07-24 至 2010-06-30
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Cancer patients are often told that they have "no evidence of disease" after initial therapy. Yet, it is crucial for these "cured" patients (pts) to have careful follow-up and monitoring for recurrence. Unfortunately, by the time such recurrence is detected by scan or symptoms, it is often too late for curative intervention. Here we propose to use molecular markers to detect minimal residual disease (MRD) immediately after completion of therapy. We use as our model metastatic neuroblastoma (NB), an orphan childhood cancer that is difficult to cure because of its tendency to relapse after near complete remission. We propose to target subclinical NB as an alternative to the traditional approach of waiting for signs or symptoms of gross disease. Doing so requires an accurate quantification of MRD in order to: (1) detect recurrence much earlier than the conventional clinicopathological methods and (2) use early response indicators for timely treatment interventions. Development of MRD measurement will also facilitate (3) assessment of the efficacy of novel therapies. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) is a highly sensitive method for measuring transcripts from viable tumor cells circulating in bone marrow (BM), peripheral blood (PB), and stem cell harvests. We have demonstrated that GD2 synthase and tyrosine hydroxylase (TH) are useful MRD markers. Nevertheless, given the heterogeneity among and within NB, studying multiple markers will enhance detection. Using tumor expression-arrays, we discovered cyclin D1 (CCND1) as a highly promising MRD marker. We propose to test the clinical utility of a core marker set (GD2synthase,TH, CCND1) for measuring MRD in 136 pts undergoing adjuvant therapy by using archived samples in the R21 phase, and prospectively collected fresh samples in 129 pts for the R33 phase. We will also complete the analysis and validation of the remaining 10 novel markers discovered by expression array analysis. Besides proving their utility as accurate measures of MRD, this application tests the hypothesis of using early MRD response for prognostication, potentially providing a guide for choosing therapies. We also aim to accelerate technology transfer to the clinic by validating one-step BM and PB sampling methods. Armed with the tools to collect samples expeditiously and to measure MRD accurately, the paradigm of treating subclinical NB can then be tested in multicenter randomized studies.
描述(由申请人提供): 癌症患者经常被告知,他们在最初的治疗后“没有疾病的证据”。然而,对这些“治愈”的患者(pts)进行仔细的随访和监测复发至关重要。不幸的是,当通过扫描或症状检测到这种复发时,对于治疗性干预来说往往为时已晚。在这里,我们建议使用分子标记物检测微小残留病(MRD)完成治疗后立即。我们使用转移性神经母细胞瘤(NB)作为我们的模型,这是一种难以治愈的孤儿儿童癌症,因为它在接近完全缓解后有复发的趋势。我们建议将亚临床NB作为等待严重疾病体征或症状的传统方法的替代方案。这样做需要准确量化MRD,以便:(1)比传统临床病理学方法更早地检测复发,以及(2)使用早期反应指标进行及时的治疗干预。MRD测量的发展也将有助于(3)评估新疗法的疗效。定量逆转录-聚合酶链反应(qRT-PCR)是一种高灵敏度的方法,用于测量骨髓(BM)、外周血(PB)和干细胞收获物中循环的活肿瘤细胞的转录物。我们已经证明,GD 2合酶和酪氨酸羟化酶(TH)是有用的MRD标记。然而,鉴于NB之间和NB内的异质性,研究多个标记将提高检测。利用肿瘤表达阵列,我们发现细胞周期蛋白D1(CCND 1)是一个非常有前途的MRD标志物。我们建议通过使用R21期存档样本和R33期前瞻性收集129例患者的新鲜样本,测试核心标志物集(GD 2合酶、TH、CCND 1)用于测量136例接受辅助治疗患者的MRD的临床效用。我们还将完成对通过表达阵列分析发现的其余10个新标记的分析和验证。除了证明它们作为MRD准确测量的实用性外,该应用程序还测试了使用早期MRD反应进行验证的假设,可能为选择治疗提供指导。我们还旨在通过验证一步BM和PB采样方法来加速技术向临床的转移。有了快速收集样本和准确测量MRD的工具,治疗亚临床NB的范例可以在多中心随机研究中进行测试。

项目成果

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NAI-KONG V CHEUNG其他文献

NAI-KONG V CHEUNG的其他文献

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{{ truncateString('NAI-KONG V CHEUNG', 18)}}的其他基金

Dual targeting of tumoral microenvironment and tumoral cells by blocking the IL-33/ST2 pathway
通过阻断 IL-33/ST2 通路双重靶向肿瘤微环境和肿瘤细胞
  • 批准号:
    10228863
  • 财政年份:
    2020
  • 资助金额:
    $ 13.3万
  • 项目类别:
Targeting Neuroblastoma with armed T cells
用武装 T 细胞靶向神经母细胞瘤
  • 批准号:
    9325268
  • 财政年份:
    2016
  • 资助金额:
    $ 13.3万
  • 项目类别:
Targeting Neuroblastoma with armed T cells
用武装 T 细胞靶向神经母细胞瘤
  • 批准号:
    9344287
  • 财政年份:
    2016
  • 资助金额:
    $ 13.3万
  • 项目类别:
Targeting Neuroblastoma with armed T cells
用武装 T 细胞靶向神经母细胞瘤
  • 批准号:
    8760348
  • 财政年份:
    2014
  • 资助金额:
    $ 13.3万
  • 项目类别:
Targeting Neuroblastoma with armed T cells
用武装 T 细胞靶向神经母细胞瘤
  • 批准号:
    8926911
  • 财政年份:
    2014
  • 资助金额:
    $ 13.3万
  • 项目类别:
Phase I Study of Humanized 3F8 Monoclonal Antibody (Hu3F8) in Patients with High-
人源化 3F8 单克隆抗体 (Hu3F8) 在高危人群中的 I 期研究
  • 批准号:
    8270451
  • 财政年份:
    2011
  • 资助金额:
    $ 13.3万
  • 项目类别:
Phase I Study of Humanized 3F8 Monoclonal Antibody (Hu3F8) in Patients with High-
人源化 3F8 单克隆抗体 (Hu3F8) 在高危人群中的 I 期研究
  • 批准号:
    8189124
  • 财政年份:
    2011
  • 资助金额:
    $ 13.3万
  • 项目类别:
A novel set of molecular markers to measure metastatic neuroblastoma
一套用于测量转移性神经母细胞瘤的新型分子标记物
  • 批准号:
    7023377
  • 财政年份:
    2006
  • 资助金额:
    $ 13.3万
  • 项目类别:
Modulation by Botanicals of Antibody Based Cancer Immuno
基于抗体的癌症免疫的植物调节
  • 批准号:
    6946043
  • 财政年份:
    2005
  • 资助金额:
    $ 13.3万
  • 项目类别:
Project 4
项目4
  • 批准号:
    7129450
  • 财政年份:
    2005
  • 资助金额:
    $ 13.3万
  • 项目类别:

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