Feline oral squamous cell carcinoma (OSCC) is a devastating tumor that is highly resistant to therapy. Cats diagnosed with OSCC have median survival times of 2-4 months. While this tumor is the most common oral tumor in cats, our understanding of mechanisms contributing to its pathogenesis is limited. There is evidence suggesting that this cancer is similar to human head and neck squamous cell carcinomas. One signaling pathway important to the human disease counterpart is the Hedgehog pathway. There are no published reports investigating the role of the Hedgehog pathway in feline OSCC. This proposed pilot study aims to investigate the role of Hedgehog signaling in feline OSCC. To fulfill this objective, we will characterize the expression of major Hedgehog pathway components (Shh, Smo, Ptch, and Gli1) in feline OSCC tissues and evaluate the significance of this pathway in vitro utilizing feline OSCC cell lines. We propose to characterize the expression of these pathway components using immunohistochemistry from tumors and correlate results with patient outcome data. We will evaluate the expression of Hedgehog target genes in feline OSCC cell lines utilizing Western blot and quantitative RT-PCR. We can study the results of Hedgehog activation or inhibition in these cell lines through treatments with Sonic Hedgehog ligand or an inhibitor of the pathway, evaluating the subsequent effects on target gene expression, cell proliferation, and survival. Resulting support for our hypothesis would provide a foundation for the design of trials utilizing targeted Hedgehog therapeutics for feline OSCC.