Infant and Toddler Brain Tumors

婴儿和幼儿脑肿瘤

基本信息

批准号：
8848786
负责人：
JAMES M OLSON
金额：
$ 36.52万
依托单位：
FRED HUTCHINSON CANCER RESEARCH CENTER
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-06-07 至 2016-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8848786
关键词：
Adult Age Antineoplastic Agents Attention Biological Assay Brain Neoplasms Cell Cycle Arrest Child Childhood Childhood Brain Neoplasm Clinical Clinical Research Clinical Trials Combination Drug Therapy Combined Modality Therapy Communities Critical Pathways Data Disease remission Disease-Free Survival Drug Combinations Drug Targeting Drug resistance Event Excision Failure Goals Growth Human Immunosuppression Incidence Industry Infant Informatics Kidney Knowledge Laboratories Malignant Neoplasms Malignant neoplasm of brain Modeling Molecular Molecular Profiling Mucositis Nature Needles Neoplasm Metastasis Neurocognitive Deficit Oncologist Operative Surgical Procedures Orphan Outcome Parenteral Nutrition Patients Pharmaceutical Preparations Pharmacologic Substance Pharmacology Phase Pre-Clinical Model Primitive Neuroectodermal Tumor Quality of life RNA Interference Radiation Rare Diseases Regimen Resistance Resources Rhabdoid Tumor Stem cells Survival Rate Technology Testing Therapeutic Therapeutic Agents Toddler Toxic effect Translational Research Ursidae Family Vomiting Work aggressive therapy base cancer cell cancer therapy chemotherapy clinically relevant density efficacy testing experience feeding genome-wide hearing impairment improved in vivo innovation innovative technologies interest medulloblastoma mouse model nasogastric feeding neoplastic cell neuro-oncology new therapeutic target novel strategies pre-clinical preclinical study therapeutic target tissue culture tumor

项目摘要

DESCRIPTION (provided by applicant): Despite aggressive treatment with surgery, combination chemotherapy with stem cell rescue, and in some cases radiation, young children with malignant brain tumors have a 5-year event-free survival rate of 15-30%. A critical barrier to more effective and less toxic therapies for these children is the paucity of functional knowledge about the molecular pathways that are critical for survival of these age-specific tumors. Furthermore, the incidence of infant and toddler brain tumors is low enough that they are orphan diseases, which attract no appreciable industry interest. In this proposal, we bring together some of the world's leading experts on high throughput RNAi assays to identify candidate therapeutic targets with an innovative new approach to test and prioritize potentially synergistic combination therapies and a highly experienced brain tumor translational research team to solve the specific clinical problem that highly aggressive therapies are failing to improve outcomes in infants and toddlers with brain tumors. Our broad, long-term goal is to double the cure rate for infants and toddlers with brain cancer. Our specific aims are 1) To assess the efficacy of Cdk 4/6 inhibition in clinically relevant mouse models of ATRT and medulloblastoma; 2) To identify novel therapeutic targets in infant and toddler brain tumors; 3) To advance one highly effective drug combination to the point of human clinical trials for infants and toddlers with brain tumors. The expected outcome is a combination therapy regimen that produces durable remission in established, bulky, clinically relevant mouse models of infant and toddler brain cancer. The significance of this work is that pediatric neuro-oncologists will abandon the highly toxic and ineffective therapeutic regimens that we are currently using in favor of a targeted approach that has higher efficacy and less toxicity.

描述（由申请人提供）：尽管对手术进行了积极的治疗，与干细胞救援的联合化疗以及在某些情况下进行的辐射，但患有恶性脑肿瘤的幼儿无事件生存率为5年，为15-30％。这些儿童更有效和毒性疗法的关键障碍是对这些分子途径的功能知识很少，这对于这些年龄特异性肿瘤的生存至关重要。此外，婴儿和幼儿脑肿瘤的发病率足够低，以至于它们是孤儿疾病，这些疾病没有引起明显的行业兴趣。 In this proposal, we bring together some of the world's leading experts on high throughput RNAi assays to identify candidate therapeutic targets with an innovative new approach to test and prioritize potentially synergistic combination therapies and a highly experienced brain tumor translational research team to solve the specific clinical problem that highly aggressive therapies are failing to improve outcomes in infants and toddlers with brain tumors.我们广泛的长期目标是使婴儿和幼儿患有脑癌的治愈率增加一倍。我们的具体目的是1）评估CDK 4/6抑制在ATRT和髓母细胞瘤的临床相关小鼠模型中的功效； 2）确定婴儿和幼儿脑肿瘤中的新型治疗靶标； 3）将一种高效的药物组合推向了针对患有脑肿瘤的婴儿和幼儿的人类临床试验。预期的结果是一种联合疗法方案，该方案在婴儿和幼儿脑癌的既定，庞大，临床相关的小鼠模型中会产生持久的缓解。这项工作的意义在于，小儿神经肿瘤学家将放弃我们目前正在使用的剧毒和无效治疗方案，而这些治疗方案有利于具有较高疗效和毒性较小的目标方法。