Admin-Core-001

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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.