Admin-Core-001

管理核心-摘要拟议的获得性治疗抵抗和铁（阿尔蒂）中心的重点是铁凋亡在获得性放射治疗抵抗中的作用。放射疗法用于治疗大约50%的癌症患者，并且是肺癌和食管癌患者的标准护理治疗。阿尔蒂中心将专注于这些癌症类型，并包括三个研究项目。项目1将集中于确定铁凋亡在获得性放射治疗抵抗中的机制，并测试铁凋亡诱导剂（FNs）作为放射增敏剂。项目2将重点确定缺氧诱导的对铁凋亡的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将集中于了解基因组和微环境因素在食管腺癌对放化疗获得性铁凋亡抵抗中的作用。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，评估使用联合疗法克服获得性辐射抗性的能力（例如，FINS与放射疗法或免疫疗法），鉴定肿瘤内缺氧区域，并评估骨髓细胞扩增在赋予铁凋亡对放化疗的抵抗性中的作用。为了支持MIC和这三个项目，将建立行政核心（AC），作为阿尔蒂中心基础设施的一部分，支持、协调和促进旨在实现和评估跨项目和核心的里程碑的所有活动。AC将在目标1中建立并保持阿尔蒂中心、ARTNet成员和项目官员之间的联系和沟通。在目标2中，咨询委员会将促进对阿尔蒂中心的评估，支持及时和高质量地编制和提交进度报告，并保持资金的适当和透明管理。AC将为目标3中的试点和跨网络项目制定和实施内部招标和优先级排序流程。在目标4中，AC将作为建立网站和管理数据、材料、资源、冲突解决以及技术和工具知识产权问题的中央基础设施。阿尔蒂中心的多名主要研究者（mPI）Boyi Gan，PhD和Albert Koong，MD，PhD将担任AC联合负责人。在他们的领导下，AC将能够利用机构和部门资源;建立和维护一个阿尔蒂中心咨询委员会;鼓励初级教师，学员和学生在癌症研究中的发展;促进整个ARTNet的合作;并确保遵守ARTNet治理和资源与数据共享政策。总的来说，AC将是阿尔蒂中心与其他ARTNet中心以及其他国家癌症研究所资助的项目和倡议整合的中心枢纽。

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.