Bone Marrow Micrometastatic Disease in Ewing Sarcoma

尤文肉瘤的骨髓微转移病

• 批准号: 8535679
• 负责人: Steven DuBois
• 金额: $ 16.4万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-16 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8535679
• 关键词: Accounting; Affect; Applications Grants; Award; Biological Assay; Biological Markers; Bone Marrow; Bone Marrow Neoplasms; California; Cells; Characteristics; Chemotherapy-Oncologic Procedure; Child; Childhood; Childhood Solid Neoplasm; Children' s Oncology Group; Clear Cell; Clinical; Clinical Research; Data; Detection; Development; Development Plans; Developmental Therapeutics Program; Disadvantaged; Disease; EWSR1 gene; Evaluation; Ewings sarcoma; Flow Cytometry; Future; Goals; Growth; Immunophenotyping; Individual; Individual Differences; Insulin-Like-Growth Factor I Receptor; International; Knowledge; Lead; Learning; Localized Disease; Malignant Bone Neoplasm; Malignant Neoplasms; Measures; Mediating; Mentored Patient-Oriented Research Career Development Award; Mentors; Metabolic Clearance Rate; Methods; Monoclonal Antibodies; Newly Diagnosed; Outcome; PTPRC gene; Patients; Pediatric Oncologist; Pharmaceutical Preparations; Pharmacogenomics; Phase; Phase III Clinical Trials; Polymerase Chain Reaction; Population; Progression-Free Survivals; Receptor Signaling; Relapse; Reliance; Research; Research Training; Risk; Role; San Francisco; Signal Pathway; Signal Transduction; Solid; Stratification; Techniques; Testing; Therapeutic Human Experimentation; Time; Training; Transcript; Universities; Validation; Variant; base; bone; burden of illness; cancer cell; career development; chemotherapy; clinically relevant; design; experience; high risk; improved; molecular marker; multidisciplinary; neoplastic cell; novel; novel marker; oncology; outcome forecast; phase 3 study; prognostic; programs; public health relevance; response; tool; translational study; tumor; young adult

DESCRIPTION (provided by applicant): This application for a K23 award contains two complementary components: a career development plan and a research plan. The career development plan will support critical additional training for the candidate, Dr. Steven DuBois, a pediatric oncologist at the University of California, San Francisco (UCSF). Dr. DuBois has used his previous training to develop a burgeoning developmental therapeutics research program focused on pediatric solid tumors. Given the increasing role of biomarkers in early phase clinical studies, Dr. DuBois now requires specific training in biomarker development and validation. He will use his flow cytometry-based marker of bone marrow micrometastatic disease in patients with Ewing sarcoma as a platform on which to obtain additional didactic and hands-on training in flow cytometry and phospho-flow cytometry. He will also complete dedicated training focused on other techniques for detecting micrometastatic disease, molecular markers in oncology, and pharmacogenomics. Dr. DuBois has assembled an outstanding team of multidisciplinary mentors to facilitate his training and research. Dr. Katherine Matthay, an international expert in clinical and translational studies in pediatric solid tumors, will serve as primary mentor. She will oversee the overall training and research plans, providing her wealth of experience in this field. Dr. Mignon Loh will provide her expertise on the use of phospho-flow cytometry to study intracellular signaling in cancer cells. Dr. Elizabeth Sinclair will provide her expertise in the use of flow cytometry to detect rare populations of cells. The research plan focuses on a flow cytometry-based technique for detecting occult tumor cells in the bone marrow of patients with Ewing sarcoma. Dr. DuBois developed this technique and his preliminary studies demonstrate that bone marrow micrometastatic disease is nearly universal in patients with Ewing sarcoma, though the number of tumor cells varies widely between patients. In Aim 1 of this application, he proposes to assess the magnitude of the association between progression-free survival and baseline bone marrow tumor cells in untreated patients with Ewing sarcoma. In Aim 2, he will determine the clearance rate of bone marrow tumor cells detected by flow cytometry in patients with Ewing sarcoma. In Aim 3, he will evaluate the ability of flow cytometry to interrogate insulin-like growth factor-1 receptor (IGF-1R) signaling pathways in occult bone marrow Ewing sarcoma cells. Incorporation of this assay into his current flow cytometry assay will allow a clinically-relevant signaling pathway to be studied in bone marrow tumor cells. The proposed studies will provide additional data needed to support an R01 application to study bone marrow micrometastatic disease as a tool for risk-stratification in a national phase III clinical trial for Ewing sarcoma.

描述（由申请人提供）：K23奖项的申请包含两个补充部分：职业发展计划和研究计划。职业发展计划将支持候选人Steven DuBois博士的关键额外培训，Steven DuBois博士是加州大学旧金山分校弗朗西斯科（UCSF）的儿科肿瘤学家。杜波依斯博士利用他以前的培训，开发了一个新兴的发展治疗研究计划，重点是儿科实体瘤。鉴于生物标志物在早期临床研究中的作用越来越大，DuBois博士现在需要在生物标志物开发和验证方面进行专门培训。他将使用他的基于流式细胞术的尤文肉瘤患者骨髓微转移疾病标记物作为平台，在此平台上获得流式细胞术和磷酸流式细胞术的额外教学和实践培训。他还将完成专门的培训，重点是检测微转移疾病的其他技术、肿瘤学分子标记物和药物基因组学。杜波依斯博士组建了一支由多学科导师组成的优秀团队，以促进他的培训和研究。凯瑟琳马泰博士，在儿科实体瘤的临床和转化研究的国际专家，将担任主要导师。她将监督整个培训和研究计划，提供她在这一领域的丰富经验。Mignon洛博士将提供她在使用磷酸流式细胞术研究癌细胞胞内信号方面的专业知识。伊丽莎白·辛克莱博士将提供她在使用流式细胞术检测罕见细胞群方面的专业知识。该研究计划的重点是基于流式细胞术的技术，用于检测尤文肉瘤患者骨髓中的隐匿性肿瘤细胞。DuBois博士开发了这项技术，他的初步研究表明，骨髓微转移疾病在尤文肉瘤患者中几乎是普遍的，尽管肿瘤细胞的数量在患者之间差异很大。在本申请的目的1中，他提出评估未治疗的尤文肉瘤患者的无进展生存期与基线骨髓肿瘤细胞之间的相关性程度。在目标2中，他将确定尤文肉瘤患者通过流式细胞术检测的骨髓肿瘤细胞的清除率。在目标3中，他将评估流式细胞术在隐性骨髓尤文肉瘤细胞中询问胰岛素样生长因子-1受体（IGF-1 R）信号通路的能力。将该测定法并入他目前的流式细胞术测定法将允许在骨髓肿瘤细胞中研究临床相关的信号传导途径。拟议的研究将提供支持R 01申请所需的额外数据，以研究骨髓微转移疾病，作为尤文肉瘤国家III期临床试验中风险分层的工具。

项目成果

Comparison of Latino and non-Latino patients with Ewing sarcoma.

拉丁裔和非拉丁裔尤文肉瘤患者的比较。

• DOI: 10.1002/pbc.24745
• 发表时间: 2014-02
• 期刊: PEDIATRIC BLOOD & CANCER
• 影响因子: 3.2
• 作者: Sharib, Jeremy;Horvai, Andrew;Hazard, Florette K. Gray;Daldrup-Link, Heike;Goldsby, Robert;Marina, Neyssa;DuBois, Steven G.
• 通讯作者: DuBois, Steven G.