Liquid biopsy approaches to inform osteosarcoma prognosis and tumor evolution

液体活检方法可告知骨肉瘤预后和肿瘤演变

基本信息

  • 批准号:
    10668427
  • 负责人:
  • 金额:
    $ 39.68万
  • 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:
    2020-07-01 至 2025-06-30
  • 项目状态:
    未结题

项目摘要

PROJECT SUMMARY/ABSTRACT Osteosarcoma is an aggressive malignancy of the bone that effects children and young adults. The current treatment standard for osteosarcoma utilizes the same chemotherapy that has been used for 30 years and outcomes have remained unchanged. Efforts to improve therapy for this disease with novel agents and treatment intensification have been largely unsuccessful. One potential reason for this is the lack of reliable prognostic biomarkers for this disease. As a result, most new candidate treatment approaches are tested in patients with relapsed or metastatic disease, excluding patients with newly diagnosed localized disease who may be at high- risk of treatment failure. Despite intensive research efforts to understand the biology of osteosarcoma, most studies have been underpowered to correlate recurrent genomic features at diagnosis with clinical outcomes. Patterns of tumor evolution that give rise to relapse have remained unstudied. Serial tumor biopsy samples for research are unavailable for evolutionary studies due to the safety concerns associated with anesthesia and surgery in children. Therefore, little is known about the genomic features of osteosarcoma that give rise to relapse. Newly available liquid biopsy technologies enable the detection of circulating tumor DNA (ctDNA) in the blood of patients with cancer. In some malignancies, ctDNA levels correlate with prognosis and changes in ctDNA levels correspond to disease response and progression. In this project, a large collection of blood samples from patients with osteosarcoma will be used to study the correlation between ctDNA levels and outcomes in newly diagnosed localized osteosarcoma and validate ctDNA as a new prognostic biomarker. Circulating tumor cells (CTCs) can also be isolated from the peripheral blood of patients with osteosarcoma and provides an alternative source of tumor cells for profiling when tumor samples are not available. In this study, CTCs from patients with osteosarcoma will be captured for single-cell profiling of tumor cells. Together with deep sequencing of ctDNA, serial samples will be used to identify recurrent patterns of tumor heterogeneity and disease evolution in osteosarcoma. These studies will fundamentally broaden the understanding of the osteosarcoma genome, the natural history of the disease, and validate novel biomarkers of outcome that could alter the way we treat patients with osteosarcoma in the near future.
项目总结/摘要 骨肉瘤是一种侵袭性骨恶性肿瘤,影响儿童和年轻人。当前 骨肉瘤的治疗标准使用了已经使用了30年的相同化疗, 结果保持不变。用新的药物和治疗方法改善这种疾病的治疗的努力 强化基本上是不成功。一个潜在的原因是缺乏可靠的预后 这种疾病的生物标志物。因此,大多数新的候选治疗方法都是在以下患者中进行测试的: 复发性或转移性疾病,不包括新诊断的局部疾病患者,这些患者可能处于高- 治疗失败的风险。 尽管密集的研究努力,以了解骨肉瘤的生物学,大多数研究已经 诊断时复发的基因组特征与临床结果的相关性不足。肿瘤类型 导致复发的进化仍然没有研究。用于研究的系列肿瘤活检样本是 由于与麻醉和手术相关的安全性问题, 孩子因此,很少有人知道的基因组特征的骨肉瘤,引起复发。 新的液体活检技术能够检测血液中的循环肿瘤DNA(ctDNA), 癌症患者。在某些恶性肿瘤中,ctDNA水平与预后和ctDNA水平的变化相关 对应于疾病的反应和进展。在这个项目中,大量收集病人的血液样本, 将用于研究ctDNA水平与新诊断骨肉瘤患者结局之间的相关性。 局部骨肉瘤和验证ctDNA作为一种新的预后生物标志物。 循环肿瘤细胞(CTC)也可以从骨肉瘤患者的外周血中分离, 提供了一种肿瘤细胞的替代来源,用于在肿瘤样本不可用时进行分析。在本研究中, 将捕获来自骨肉瘤患者的CTC用于肿瘤细胞的单细胞分析。与深 ctDNA测序,系列样品将用于鉴定肿瘤异质性的复发模式, 骨肉瘤的疾病演变。这些研究将从根本上拓宽对 骨肉瘤基因组,疾病的自然史,并验证新的生物标志物的结果, 在不久的将来改变我们治疗骨肉瘤患者的方式。

项目成果

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Brian Crompton其他文献

Brian Crompton的其他文献

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{{ truncateString('Brian Crompton', 18)}}的其他基金

PROJECT 3: Applying Liquid Biopsy Technologies to Detect Clinical Response and Mechanisms of Resistance in the Treatment of LMS
项目 3:应用液体活检技术检测 LMS 治疗的临床反应和耐药机制
  • 批准号:
    10493631
  • 财政年份:
    2022
  • 资助金额:
    $ 39.68万
  • 项目类别:
PROJECT 3: Applying Liquid Biopsy Technologies to Detect Clinical Response and Mechanisms of Resistance in the Treatment of LMS
项目 3:应用液体活检技术检测 LMS 治疗的临床反应和耐药机制
  • 批准号:
    10705742
  • 财政年份:
    2022
  • 资助金额:
    $ 39.68万
  • 项目类别:
Liquid biopsy approaches to inform osteosarcoma prognosis and tumor evolution
液体活检方法可告知骨肉瘤预后和肿瘤演变
  • 批准号:
    10202511
  • 财政年份:
    2020
  • 资助金额:
    $ 39.68万
  • 项目类别:
Liquid biopsy approaches to inform osteosarcoma prognosis and tumor evolution
液体活检方法可告知骨肉瘤预后和肿瘤演变
  • 批准号:
    10426209
  • 财政年份:
    2020
  • 资助金额:
    $ 39.68万
  • 项目类别:
Targeting FAK and integrin signaling in preclinical models of Ewing sarcoma
尤文肉瘤临床前模型中针对 FAK 和整合素信号传导
  • 批准号:
    9512891
  • 财政年份:
    2015
  • 资助金额:
    $ 39.68万
  • 项目类别:
Targeting FAK and integrin signaling in preclinical models of Ewing sarcoma
尤文肉瘤临床前模型中针对 FAK 和整合素信号传导
  • 批准号:
    8967409
  • 财政年份:
    2015
  • 资助金额:
    $ 39.68万
  • 项目类别:

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