(PQ6) Molecular Mechanisms of Dormancy in MYC-Driven Medulloblastoma

(PQ6) MYC 驱动的髓母细胞瘤休眠的分子机制

• 批准号: 8922703
• 负责人: Yanxin Pei
• 金额: $ 18.14万
• 依托单位: CHILDREN'S RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-06 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8922703
• 关键词: Affect; Aftercare; Animal Model; Animals; Apoptosis; Astrocytes; Cell Cycle; Cells; Characteristics; Child; Childhood Malignant Brain Tumor; Development; Disease; Event; Exhibits; Gene Expression; Gene Expression Profile; Genetic; Goals; Growth; Health; High Dose Chemotherapy; In Situ; In Vitro; Incidence; Knowledge; Lead; Malignant Neoplasms; Malignant neoplasm of brain; Mediator of activation protein; Mitotic; Modeling; Molecular; Molecular Profiling; Neurons; Oncogenes; Outcome; Pathway interactions; Patients; Poison; Population; Proliferating; Property; Radiation; Radiosurgery; Recurrence; Regimen; Relapse; Signal Pathway; Signal Transduction; Stimulus; Survival Rate; Testing; Time; Toxic effect; base; chemotherapy; disorder subtype; effective therapy; gene function; improved; in vivo; insight; medulloblastoma; neoplastic cell; nerve stem cell; novel; novel strategies; overexpression; prevent; programs; small molecule; small molecule libraries; stem cell biology; stem cell differentiation; stem cells; therapy resistant; tool; tumor; tumor growth

DESCRIPTION (provided by applicant): Medulloblastoma (MB) is the most common malignant brain tumor in children. Although surgery, radiation and high-dose chemotherapy have led to increased survival rates, many MB patients still die from their disease, in part due to the high incidence of tumor recurrence. Thus, novel and more effective therapies for MB are critically important. The most aggressive subtype of MB consists of tumors that exhibit overexpression or amplification of the MYC oncogene. Patients with MYC-driven MB initially to respond to therapy, but then relapse months or years later, suggesting that some tumor cells can persist, and remain dormant for prolonged periods after treatment. However, the molecular basis of this dormancy, and the events that lead to tumor recurrence, remain unclear. We recently developed a unique model of MYC-driven MB that allows us to induce dormancy, to identify and isolate dormant tumor cells (DTCs), and to compare these cells to the normal stem cells from which they arise. Using this model, we propose to: (1) Determine whether DTCs resemble stem cells phenotypically and functionally, (2) Identify the molecular mechanisms of tumor cell dormancy by comparing the gene expression profiles of DTCs, stem cells and malignant tumor cells, and (3) Screen for small molecules that promote differentiation of dormant tumor cells, but are not toxic to normal stem cells. If these studies are successful, they will help identify novel approaches to preventing tumor relapse in MYC-driven MB and other malignancies. !

描述（申请人提供）：髓母细胞瘤（Medulloblastoma， MB）是儿童最常见的恶性脑肿瘤。尽管手术、放疗和大剂量化疗提高了患者的存活率，但许多MB患者仍然死于他们的疾病，部分原因是