PROJECT SUMMARY The Wisconsin Head and Neck SPORE is designed to promote translational laboratory and clinical research to improve overall outcome for patients with Head and Neck Cancer (HNC). This highly collaborative research links basic scientists with HNC clinicians to advance novel treatment strategies for this complex cancer popoulation. These patients bear a disproportionate burden from their cancers based on the critical anatomic location of the disease where treatment can compromise speech, swallow, and breathing function, in addition to creating significant alterations in physical appearance and capacity for social interaction. Efforts to improve cure rates must be carefully balanced with efforts to reduce treatment morbidity to enable enhanced overall quality of life for patients. The broad objectives of this SPORE are to: 1) Promote multidisciplinary translational research in HNC, 2) Improve overall survival and quality of life for patients with HNC, 3) Develop new animal model systems of HNC to test novel targeted therapy strategies, 4) Develop common resources (such as patient-derived tumor xenografts) to be shared across institutions to promote translational research, and 5) Translate promising new molecules developed at the University of Wisconsin through preclinical and clinical testing. The Wisconsin HN SPORE has designed four primary research projects. Project 1 will define and target molecular pathways that drive HNC using new mouse model systems, and identify biomarkers of prognostic value for clinical investigation. Project 2 will examine a novel, tumor-selective radiolabeled molecule developed at UW that internally targets HN tumors with radiation and shows potential to reduce toxicity from conventional treatment. Project 3 investigates molecular targeting of HNC with novel synstatin peptide therapeutics that disrupt signaling complexes coupled to receptor tyrosine kinases. Project 4 investigates the role of the receptor tyrosine kinase AXL in HNC therapy response and resistance to help design more effective future treatment strategies. The Wisconsin SPORE will support this research with three Cores (Administrative, Pathology and Biostatistics), a Career Enhancement Program and a Developmental Research Program.