Admin-Core-001

拟议的获得性治疗和铁耐药性（ARTI）中心的重点是铁下垂在获得性放射治疗耐药中的作用。放射治疗用于治疗大约50%的癌症患者，是肺癌和食管癌患者的标准护理治疗。ARTI中心将专注于这些癌症类型，并包括三个研究项目。项目1将侧重于确定铁下垂在获得性放射治疗耐药中的机制，并测试铁下垂诱导剂（FINs）作为放射增敏剂。项目2将侧重于确定缺氧诱导的铁下垂抵抗是否有助于肿瘤获得性放射治疗抵抗，以及FINs是否使缺氧肿瘤细胞对放射治疗再敏感。项目3将重点研究基因组和微环境因素在食管癌患者对放化疗获得性铁中毒耐药中的作用。这三个研究项目将由一个共享的分子成像核心（MIC）提供支持，该核心将提供成像工具和分析，用于测量肿瘤生长，评估使用联合治疗（例如，FINs与放射治疗或免疫治疗）克服获得性放射耐药的能力，识别肿瘤内缺氧区域，以及评估骨髓细胞扩增是否赋予铁下沉对放化疗的抗性。为了支持MIC和这三个项目，将建立行政核心（AC），作为ARTI中心基础设施的一部分，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。交流委员会将在目标1中建立并保持ARTI中心与ARTNet成员和项目官员之间的接触和沟通。在目标2中，咨询委员会将促进ARTI中心的评估，支持及时和高质量的开发和提交进度报告，并保持适当和透明的资金管理。谘询委员会将为第三目标中的试点和跨网络项目制定和实施内部征求和优先次序程序。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心基础设施。ARTI中心的多位首席研究员（mPIs）， Boyi Gan，博士和Albert Koong， MD，博士将担任AC的共同领导。在他们的领导下，咨询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；鼓励初级教师、学员和学生在癌症研究方面的发展；促进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，交流中心将是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倡议整合的中心节点。

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.