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和最致命的实体瘤。这种肿瘤占癌症的8-10%，占儿童癌症死亡的15%。虽然三分之一的儿童在1岁以下被诊断出来，但大多数儿童在1至10岁之间被诊断出来，其中大多数患有转移性疾病，并将死于肿瘤进展。这项名为“神经母细胞瘤生物学和治疗”的计划项目资助的目标是研究神经母细胞瘤肿瘤发生和发展的关键特定生物学途径，并开发新的治疗方法， 在这些道路上。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的作用（加勒特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，负责人） 项目3。MYCN扩增的神经母细胞瘤中凋亡失调（Michael Hogarty，负责人） 项目4。类维生素A与细胞毒性剂在神经母细胞瘤中的整合（Peter Adamson，组长）。 核心动物模型和病理学核心（John Maris，核心总监;布鲁斯Pawel，联合总监） 核心生物统计学和生物信息学核心（Avital Cnaan，核心总监; Eric Rappaport，联合总监） 核心药代动力学核心（Peter Adamson，核心总监） 人们越来越关注用酪氨酸激酶抑制剂、血管生成抑制剂、细胞死亡促进剂和类维生素A治疗癌症的新方法。我们计划开发基于生物学的新疗法，并可能具有临床疗效。这些研究的成功完成应确定新的药物和药物组合，旨在重要的生长，分化和细胞死亡途径，应该是非常有效的，远远低于传统疗法的毒性。我们期望将这些治疗方法迅速进入临床试验。此外，针对神经母细胞瘤开发的治疗策略可能适用于儿童和成人中依赖生物学途径并受这些药物影响的其他肿瘤。