The Center for Therapeutic Targeting of EWS-oncoproteins

EWS癌蛋白治疗靶向中心

• 批准号: 10382013
• 负责人: SCOTT A ARMSTRONG
• 金额: $ 19.83万
• 依托单位: DANA-FARBER CANCER INST
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10382013
• 关键词: Award; Basic Science; Biology; Chemicals; Chimeric Proteins; Clinic; Clinical Research; Complex; Computational Biology; Development; Disease; EWS-FLI1 fusion protein; Epigenetic Process; Ewings sarcoma; Functional disorder; Genetic Transcription; Goals; Individual; Industrialization; Institution; Investigational Therapies; Knowledge; Malignant Neoplasms; Molecular; Oncogenic; Oncoproteins; Parents; Pediatric Oncologist; Process; Proteins; Research; Talents; Technology; Therapeutic; Therapeutic Clinical Trial; Translations; Validation; bone; clinical translation; drug development; improved outcome; mouse model; novel; novel therapeutics; pediatric patients; pre-clinical; sarcoma; skills; structural biology; success; therapeutic target; tool; translational scientist; tumorigenesis

PROJECT SUMMARY: Overall This section is unchanged from the U54 CA231637 parent award. The primary scientific focus of this Center is to understand the molecular underpinnings of EWS-ETS driven Ewing sarcoma and to investigate novel treatments and therapeutic mechanisms to improve outcomes for pediatric patients with this aggressive disease. Translation of molecular understanding of sarcoma pathophysiology into effective new drugs in the clinic is a complex, risky proposition that requires the coordinated efforts of a talented team of individuals with complementary skills. This group brings expertise in Ewing sarcoma biology and the EWS-ETS oncoproteins, epigenetics and transcription, structural biology, computational biology, chemical biology and drug development, mouse models, preclinical experimental therapeutics, and clinical trials development. A Center mechanism is essential to the success of this proposal. No one institution nor individual can bring mastery of the diversity of approaches, technologies, and scientific domains needed to achieve the goals of this proposal. We have elected to focus on understanding the fundamental inner workings of Ewing sarcoma from its transcriptional circuits, to the direct protein interactions with EWS-FLI1, to the direct and immediate effects of EWS-FLI1 degradation. Moreover, a strong emphasis of this proposal is on target identification and preclinical validation, critical steps in the process of bringing forward therapies with optimal chances for success in the clinic. The team that is assembled has all of the component pieces needed for success. Our Center includes outstanding basic cancer biologists, chemists, computational biologists, and translational researchers, and five pediatric oncologists. Thus, the proposed Center can catalyze basic discovery and clinical translation by leveraging basic and clinical research talent within the Center and our strong ties to outside academic and industrial partners.

项目摘要：总体 本节与U54 CA231637家长奖没有变化。 该中心的主要科学重点是了解EWS-ET的分子基础 驱动的尤因肉瘤并研究新的治疗和治疗机制以改善 患有这种侵略性疾病的小儿患者的结局。分子的翻译 在诊所中，将肉瘤的病理生理学理解成有效的新药是一个复杂，风险的 命题需要一支有才华的人团队具有互补技能的人的协调努力。 该小组带来了Ewing肉瘤生物学和EWS-ETS癌蛋白，表观遗传学和 转录，结构生物学，计算生物学，化学生物学和药物开发，小鼠 模型，临床前实验疗法和临床试验开发。中心机制是 这对于该提议的成功至关重要。没有一个机构或个人可以掌握多样性 实现该提案的目标所需的方法，技术和科学领域。我们有 当选专注于理解尤因肉瘤的基本内部运作 转录电路，直接与EWS-FLI1的直接蛋白质相互作用，直接直接直接 EWS-FLI1降解的影响。此外，该提议的强烈重视是目标 识别和临床前验证，以最佳的方式提出疗法的过程中的关键步骤 诊所成功的机会。组装的团队具有所需的所有组成部分 为了成功。我们的中心包括出色的基本癌症生物学家，化学家，计算生物学家， 和翻译研究人员和五位儿科肿瘤学家。因此，提出的中心可以催化基本 通过利用该中心和我们的基本和临床研究才能的发现和临床翻译 与外部学术和工业合作伙伴的牢固联系。