Neuroendocrine Tumor Specialized Programs of Research Excellence (SPORE) in Human Cancer - Overall – Summary Neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs) are orphan cancers whose incidence and prevalence are increasing in the US. NETs are slow-growing, yet relentlessly progressive and are notoriously resistant to chemotherapy. The University of Iowa is one of only a handful of institutions where patients with NETs and NECs are diagnosed, treated, and followed comprehensively over time by an interdisciplinary team that includes both clinical and laboratory-based investigators with a focused interest in these tumors. This SPORE will support innovative translational NET research through three projects: 1. Project 1 is a multi-institutional investigation of a new strategy to sensitize pNETs to immune checkpoint inhibitor (ICI) therapy culminating in a Phase 1b window of opportunity trial combining CDK4/6 inhibitor therapy with ICI therapy in pNET patients. 2. Project 2 combines pre-clinical metabolic studies of radiation-induced lipid peroxidation with a Phase 1 alpha-emitter radiation therapy trial using 212Pb Pentixather targeting C-X-C Receptor 4 (CXCR4) in lung NETs and NECs. 3. Project 3 is a timely investigation of the tumor-promoting potential of GLP1 and GIP receptor agonists in gastroenteropancreatic NETs as those agents have burgeoning clinical use and unprecedented levels of patient interest. The Iowa NET SPORE will support translational investigators through four interactive cores: A. The Administrative Core facilitates communication and collaboration between projects, cores, external colleagues, advisors and patient advocates. B. The Biospecimens Core provides access to multiple sources of rare NET tissue and guides scientific use and accurate tumor classification. C. The Biostatistics Core provides study design, data analysis, quality control and biostatistics education. D. The Clinical Core provides access to data in the NET Registry on >2,400 identified patients eager to participate in trials as well as clinical trial coordination and regulatory support to projects. We will recruit NET translational researchers via developmental research and career enhancement programs that successfully transition junior scientists to independent funding and introduce established scientists to the NET field. Together with patients, we will promote translational research in NETs through vertical and horizontal collaborations that will lead to improved management of patients with NETs and NECs. IMPACT: Achievement of these goals will result in scientific advances related to NETs and other cancers, translation of novel molecularly targeted therapies for patients with NETs and NECs, alteration in patient management, and prolonged as well as improved quality of life for patients with NETs and NECs.
