Children's Oncology Group Chair's Grant

总体描述（由申请人提供）：儿童肿瘤组（COG）是由四个儿科合作组统一而成的一个新的多学科临床试验组。它是世界上最大的儿童癌症研究组织，在北美、澳大利亚和欧洲的一些机构中，包括大约238个儿科癌症项目作为临床试验点。它完全准备好将基础生物学研究转化为临床研究，并通过人体原理证明、毒性评估、功效鉴定，最终纳入已建立的治疗方法，以改善结果和/或降低毒性。COG代表了四个团体的遗产，其中最古老的一个已经存在了近50年。目前，48259例临床试验累积患者正在积极随访；挽救了超过250万人的生命。虽然儿童癌症死亡率在过去的二十年里下降了50%，在过去的十年里下降了25%，但仅在美国，每年就有近2500名儿童和青少年死于癌症。大多数死亡可归因于特定的儿科癌症，必须设计新的治疗方法。这些高风险癌症治愈率的提高更有可能是由于发现了预测耐药性的生物学特征，更重要的是，通过发现具有新的作用机制的新型抗癌药物，其疗效可能根据在癌细胞中检测到的特定独特分子异常来预测。COG还首次独特地建立了北美范围内基于人群的儿童癌症登记处，利用病例对照研究，调查潜在的流行病学关联，包括遗传改变以及基因与环境的最终相互作用。COG通过一系列假设驱动的研究，寻求最大限度地提高癌症儿童的治愈率；扩大对肿瘤和宿主生物学的理解；阐明新的治疗策略，建立风险调整治疗的概念；并减少治疗相关的毒性和发病率，从而优化生活质量和生存。拟议的研究旨在将儿童癌症死亡率降低20%，并在研究期间将5年无病生存率（治愈率）提高到85%。

OVERALL DESCRIPTION (provided by applicant): The Children's Oncology Group (COG) is a new multidisciplinary clinical trials group resulting form the unification of the four pediatric cooperative groups. It is the largest childhood cancer research organization in the world and encompasses approximately 238 pediatric cancer programs as clinical trial sites throughout all of North America, Australia, and several institutions in Europe. It is exclusively well poised to translate basic biology studies into clinical investigations and to develop translational approaches through human proof of principle, toxicity assessment, identification of efficacy, and ultimately, incorporation into established treatments to improve outcome and/or decrease toxicity. COG represents the legacy of four groups, the oldest of which existed for nearly 50 years. Currently, 48,259 patients accrued to clinical trials are in active follow-up; over 2,500,000 person years of life have been saved. Although childhood cancer mortality has decreased by 50 percent in the last two decades and by 25 percent in the past decade, nearly 2,500 children and adolescents die from cancer annually in the U.S. alone. The majority of the deaths can be attributed to specific pediatric cancers for which new therapeutic approaches must be devised. Improvement in the cure rates for these high-risk cancers is more likely to emerge as a result of the identification of biologic features which predict resistance and, more importantly, by the identification of new anti-cancer agents with novel mechanisms of action, whose efficacy might be predicted on the basis of specific unique molecular abnormalities detected in cancer cells. COG is also uniquely able to establish for the first time a North America-wide population-based registry of childhood cancer to investigate, utilizing case control studies, potential epidemiologic associations, including genetic alterations and ultimately interactions of genes with the environment. COG, through a series of hypothesis-driven research studies, seeks to maximize cure rates for children with cancer; to achieve an expanded understanding of tumor and host biology; to elucidate new therapeutic strategies and to build on the concept of risk-adjusted therapy; and to reduce treatment-related toxicity and morbidity, thereby optimize quality of life and survival. The proposed research is aimed at reducing deaths from childhood cancer by 20 percent and increasing 5-year disease free survival (cure) rates to >85 percent during the study period.