Admin-Core-001

管理核心-001

• 批准号: 10942885
• 负责人: Boyi Gan
• 金额: $ 18.23万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10942885
• 关键词: Achievement; Administrative Supplement; Advisory Committees; Basic Science; Benchmarking; Cancer Patient; Clinical; Cloning; Collaborations; Combined Modality Therapy; Communication; Data; Development; Direct Costs; Doctor of Philosophy; Ensure; Esophageal Adenocarcinoma; Evaluation; Faculty; Funding; Genomics; Goals; Guidelines; Human; Hypoxia; Image; Imaging Device; Immunotherapy; Infrastructure; Institution; Intellectual Property; Iron; Knowledge; Leadership; Malignant neoplasm of esophagus; Malignant neoplasm of lung; Measures; Metabolic; Mus; Myeloid Cells; National Cancer Institute; Office of Administrative Management; Patients; Performance; Policies; Pre-Clinical Model; Principal Investigator; Process; Production; Progress Reports; Radiation; Radiation therapy; Radiation-Sensitizing Agents; Reporter Genes; Research; Research Project Grants; Resistance; Resource Sharing; Resources; Risk; Role; Sampling; Students; Technology; Testing; Therapeutic Agents; Training; Transfection; Transgenic Organisms; Translating; Translational Research; Wages; Work; Xenograft Model; anticancer research; cancer cell; cancer type; chemoradiation; cohort; conflict resolution; data management; data sharing; esophageal cancer patient; interest; meetings; member; molecular imaging; neoplastic cell; novel therapeutics; outreach; peer; programs; radiation resistance; stable cell line; standard of care; therapy resistant; tool; tumor; tumor growth; tumor hypoxia; web site

ADMINISTRATIVE CORE – SUMMARY The proposed Acquired Resistance to Therapy and Iron (ARTI) Center is focused on the role of ferroptosis in acquired resistance to radiation therapy. Radiation therapy is used to treat approximately 50% of cancer patients and is standard of care treatment for lung cancer and esophageal cancer patients. The ARTI Center will focus on these cancer types and comprise three research projects. Project 1 will focus on identifying the mechanisms of ferroptosis in acquired resistance to radiation therapy and testing ferroptosis inducers (FINs) as radiosensitizers. Project 2 will focus on determining whether hypoxia-induced resistance to ferroptosis contributes to acquired tumor resistance to radiation therapy and whether FINs re-sensitize hypoxic tumor cells to radiation treatment. Project 3 will focus on understanding the role of genomic and microenvironment factors in acquired resistance to ferroptosis to chemoradiation in esophageal adenocarcinoma. The three research projects will be supported by one shared Molecular Imaging Core (MIC), which will provide imaging tools and analyses for measuring tumor growth, assessing the ability to overcome acquired radiation resistance using combination therapies (e.g., FINs with radiation therapy or immunotherapy), identifying intratumoral hypoxic regions, and evaluating myeloid cell expansion in conferring ferroptosis resistance to chemoradiation therapy. To support the MIC and these three projects, the Administrative Core (AC) will be established as part of the ARTI Center infrastructure that will support, coordinate, and facilitate all activities aimed at achieving and evaluating milestones across the projects and core. The AC will establish and maintain engagement and communication among ARTI Center and ARTNet members and program officials in Aim 1. In Aim 2, the AC will facilitate ARTI Center evaluation, support the timely and quality development and submission of progress reports, and maintain proper and transparent stewardship of funds. The AC will develop and implement an internal solicitation and prioritization process for Pilot and Trans-Network Projects in Aim 3. In Aim 4, the AC will serve as the central infrastructure to build a website and manage data, materials, resources, conflict resolution, and issues of intellectual property for technologies and tools. The multiple Principal Investigators (mPIs) of the ARTI Center, Boyi Gan, PhD and Albert Koong, MD, PhD, will serve as AC Co-Leaders. Under their leadership, the AC will be able to leverage institutional and divisional resources; to establish and maintain an ARTI Center Advisory Committee; to encourage the development of junior faculty, trainees, and students in cancer research; to promote collaborations across ARTNet; and to ensure abidance by the ARTNet governance and resource and data sharing policies. Overall, the AC will be the central juncture for the ARTI Center to integrate with other ARTNet centers as well as other National Cancer Institute-funded programs and initiatives.

管理核心 – 摘要 拟议的获得性治疗和铁抗性 (ARTI) 中心的重点是铁死亡在获得性放射治疗抗性中的作用。放射治疗用于治疗大约 50% 的癌症患者，是肺癌和食道癌患者的标准护理治疗。 ARTI 中心将重点关注这些癌症类型，并包括三个研究项目。项目 1 将重点确定铁死亡在放射治疗获得性耐药中的机制，并测试铁死亡诱导剂 (FIN) 作为放射增敏剂。项目 2 将重点确定缺氧诱导的铁死亡抵抗是否有助于获得性肿瘤对放射治疗的抵抗，以及 FIN 是否使缺氧肿瘤细胞对放射治疗重新敏感。项目 3 将重点了解基因组和微环境因素在食管腺癌放化疗获得性铁死亡抗性中的作用。这三个研究项目将得到一个共享的分子成像核心 (MIC) 的支持，该核心将提供成像工具和分析，用于测量肿瘤生长、评估使用联合疗法（例如 FIN 联合放射治疗或免疫治疗）克服获得性放射抗性的能力、识别肿瘤内缺氧区域，以及评估赋予铁死亡对放化疗治疗抗性的骨髓细胞扩张。为了支持 MIC 和这三个项目，将建立管理核心 (AC) 作为 ARTI 中心基础设施的一部分，该基础设施将支持、协调和促进旨在实现和评估项目和核心里程碑的所有活动。在目标 1 中，AC 将在 ARTI 中心和 ARTNet 成员以及项目官员之间建立并保持参与和沟通。在目标 2 中，AC 将促进 ARTI 中心的评估，支持及时、高质量的开发和进度报告的提交，并保持适当和透明的资金管理。 AC 将为目标 3 中的试点和跨网络项目制定并实施内部征求和优先排序流程。在目标 4 中，AC 将作为中央基础设施来构建网站并管理数据、材料、资源、冲突解决以及技术和工具的知识产权问题。 ARTI 中心的多名首席研究员 (mPI) Boyi Gan 博士和 Albert Koong 医学博士、博士将担任 AC 联合领导者。在他们的领导下，审计委员会将能够利用机构和部门资源；建立并维持 ARTI 中心咨询委员会；鼓励癌症研究领域的初级教师、实习生和学生的发展；促进 ARTNet 上的合作；确保遵守 ARTNet 治理以及资源和数据共享政策。总体而言，AC 将成为 ARTI 中心与其他 ARTNet 中心以及其他国家癌症研究所资助的项目和举措整合的中心枢纽。