Neuroblastoma Biology and Therapy

神经母细胞瘤生物学和治疗

• 批准号: 6804513
• 负责人: GARRETT M BRODEUR
• 金额: $ 209.08万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-30 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6804513
• 关键词: clinical research; molecular oncology; neoplasm /cancer chemotherapy; neoplastic process; neuroblastoma

Neuroblastoma is the most common and deadly solid tumor in children. This tumor accounts for 8-10% of the cancers and 15% of the deaths from cancer in childhood. Although a third of children are diagnosed under the age of 1 year, the majority of children are diagnosed between 1 and 10 years of age, and most of these have metastatic disease and will die from tumor progression. The goal of this Program Project Grant entitled "Neuroblastoma Biology and Therapy" is to investigate specific biological pathways critical to neuroblastoma tumorigenesis and progression and to develop novel approaches to treatment that are aimed at these pathways. This program is organized into 4 projects and 4 Cores: Project 1. P75 and Trk in Neuroblastoma Differentiation and Death (Garrett Brodeur, Leader). Project 2. Antiangiogenic Strategies for Neuroblastoma Therapy (John Maris, Leader) Project 3. Deregulated Apoptosis in MYCN Amplified Neuroblastomas (Michael Hogarty, Leader) Project 4. Integration of Retinoids with Cytotoxic Agents in Neuroblastoma (Peter Adamson, Leader). Core . Animal Model and Pathology Core (John Maris, Core Director; Bruce Pawel, Co-Director) Core . Biostatistics and Bioinformatics Core (Avital Cnaan, Core Director; Eric Rappaport, Co-Director) Core . Pharmacokinetics Core (Peter Adamson, Core Director) There is increasing interest in novel approaches to cancer treatment with tyrosine kinase inhibitors, angiogenesis inhibitors, cell death-promoting agents and retinoids. We plan to develop novel therapies that are biologically based and likely to have clinical efficacy. The successful completion of these studies should identify novel agents and combinations of agents aimed at important growth, differentiation and cell death pathways that should be very effective and far less toxic than conventional therapy. We anticipate moving these treatment approaches rapidly into clinical trials. Furthermore, treatment strategies developed against neuroblastoma may be useful against other tumors in children and adults that are rely on the biological pathways and are affected by these agents.

神经母细胞瘤是儿童中最常见和致命的实体瘤。该肿瘤占癌症癌症的8-10％和15％的癌症死亡。尽管三分之一的儿童被诊断出1岁以下，但大多数儿童被诊断出1至10岁，其中大多数患有转移性疾病，并且会死于肿瘤进展。该计划项目授予的题为“神经母细胞瘤生物学和治疗”的目标是研究对神经母细胞瘤肿瘤和进展至关重要的特定生物学途径，并开发针对旨在的治疗方法 在这些途径。该计划分为4个项目和4个核心： 项目1。P75和TRK在神经母细胞瘤分化和死亡中（Garrett Brodeur，领导者）。 项目2。神经母细胞瘤疗法的抗血管生成策略（John Maris，领导者） 项目3。在MYCN扩增神经母细胞瘤中放松管凋亡（迈克尔·霍加蒂（Michael Hogarty），领导者） 项目4。在神经母细胞瘤中的类视网膜类动物与细胞毒性剂的整合（领导者彼得·亚当森（Peter Adamson））。 核 。动物模型和病理核心（核心主任约翰·马里斯（John Maris）；布鲁斯·帕维尔（Bruce Pawel），联合导演） 核 。生物统计学和生物信息学核心（Avital Cnaan，核心主任； Eric Rappaport，联合导演） 核 。药代动力学核心（彼得·亚当森（Peter Adamson），核心总监） 对使用酪氨酸激酶抑制剂，血管生成抑制剂，促进死亡死亡的剂和类维生素类似的新型癌症治疗方法的兴趣越来越大。我们计划开发基于生物学并可能具有临床功效的新型疗法。这些研究的成功完成应确定针对重要生长，分化和细胞死亡途径的新型药物和组合，这些药物应该非常有效，毒性远低于常规疗法。我们预计这些治疗方法会迅速将其转移到临床试验中。此外，针对神经母细胞瘤制定的治疗策略可能对依赖生物途径并受这些药物影响的儿童和成人的其他肿瘤有用。