Administrative Core

行政核心-摘要 拟议中的获得性治疗抵抗和铁（阿尔蒂）中心的重点是铁凋亡的作用 对放射治疗的获得性抵抗放射疗法用于治疗约50%的癌症 是肺癌和食管癌患者的标准治疗。阿尔蒂中心将 主要研究这些癌症类型，包括三个研究项目。项目1将侧重于确定 铁凋亡在获得性放射治疗抵抗中的作用机制以及铁凋亡诱导剂（FIN）的检测， 放射增敏剂。项目2将集中于确定是否缺氧诱导的抵抗铁凋亡 有助于获得性肿瘤对放射治疗的抗性以及FIN是否使缺氧肿瘤细胞重新敏感 到放射治疗项目3将侧重于了解基因组和微环境因素的作用 在食管腺癌中获得性抵抗放化疗的铁凋亡。三项研究 项目将由一个共享的分子成像核心（MIC）支持，该核心将提供成像工具， 用于测量肿瘤生长的分析，评估克服获得性辐射抗性的能力， 联合疗法（例如，FIN与放射治疗或免疫治疗），识别肿瘤内缺氧 区域，并评估骨髓细胞扩增赋予铁凋亡抵抗放化疗。 为了支持多边投资委员会和这三个项目，将设立行政核心，作为 阿尔蒂中心的基础设施，将支持，协调和促进旨在实现和 评估跨项目和核心的里程碑。AC将建立并保持接触， 阿尔蒂中心与ARTNet成员和Aim 1项目官员之间的沟通。目标2：AC将 促进阿尔蒂中心评估，支持及时和高质量的开发和提交进展 报告，并保持适当和透明的资金管理。AC将制定和实施一项 目标3中的试点和跨网络项目的内部招标和优先级排序过程。第四，AC 将作为建立网站和管理数据、材料、资源、冲突的中心基础设施， 解决方案以及技术和工具的知识产权问题。多名主要研究者 （mPI）的阿尔蒂中心，Boyi Gan，博士和阿尔伯特孔，医学博士，博士，将担任AC共同领导人。下 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;促进整个ARTNet的合作;并确保遵守ARTNet治理 以及资源和数据共享政策。总的来说，AC将是阿尔蒂中心的中心枢纽， 与其他ARTNet中心以及其他国家癌症研究所资助的计划和倡议相结合。

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.