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最常见、最致命的实体瘤。这种肿瘤占儿童癌症的8%-10%，占儿童癌症死亡的15%。虽然三分之一的儿童在1岁以下被确诊，但大多数儿童在1至10岁之间被确诊，其中大多数人患有转移性疾病，将死于肿瘤的进展。这项名为“神经母细胞瘤生物学和治疗”的项目的目标是研究神经母细胞瘤发生和发展的特定生物学途径，并开发新的治疗方法。 在这些小路上。该计划由4个项目和4个核心组成： 项目1.神经母细胞瘤分化和死亡中的p75和Trk(Garrett Brodeur，领导者)。 项目2.神经母细胞瘤治疗的抗血管生成策略(John Maris，领导者) 项目3：MYCN扩增的神经母细胞瘤中的非调控的细胞凋亡(Michael Hogarty，领导者) 项目4：神经母细胞瘤中维甲酸与细胞毒剂的整合(Peter Adamson，领导者)。 核心。动物模型和病理学核心(John Maris，核心主任；Bruce Pawel，联席主任) 核心。生物统计和生物信息学核心(核心主任阿维塔尔·克南；联席主任埃里克·拉帕波特) 核心。药代动力学核心(Peter Adamson，核心董事) 人们对酪氨酸激酶抑制剂、血管生成抑制剂、细胞死亡促进剂和维甲酸类药物治疗癌症的新方法越来越感兴趣。我们计划开发基于生物的、可能具有临床疗效的新疗法。这些研究的成功完成应该会发现针对重要的生长、分化和细胞死亡途径的新型药物和药物组合，这些药物应该非常有效，而且毒性远远低于传统疗法。我们预计这些治疗方法将迅速进入临床试验。此外，针对神经母细胞瘤开发的治疗策略可能对依赖于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。