In cats, mammary cancer accounts for up to 17% of all non-lymphoid tumors with an average age of occurrence at 10 years. Between 80 and 96% of mammary tumors in cats are malignant, and spread to other tissues. Thus, mammary cancer is a devastating disease in cats. Moreover, treatment strategies are very limited because most of the cancer growth pathways in cats are unknown. Prostaglandin E2 (PGE2), a hormone secreted by cancer tissues promotes tumor cell migration, invasion, spread, and blood vessel growth. PGE2 is synthesized through two major enzymes called COX-2 and PGES-1. An increased level of tumor-derived PGE2 and expression of COX-2 and PGES-1 are hall-marks of mammary cancer. Inhibition of COX-2 by non-steroidal anti- inflammatory drugs decreases the incidence of various cancers. Epidermal growth factor receptor (EGFR)-mediated pathways regulate PGE2 production in metastatic cancers. Therefore, targeting COX-2 and/or PGES-1 to inhibit synthesis of tumor-promoting PGE2 could be a potential target for future cancer therapies. In the present study, specific roles of COX-2/PGES-1 pathways and interactions between EGFR and COX-2/PGES-1 pathways in feline mammary cancers will be determined. This study will determine the role of PGE2 in feline mammary tumors. The critical pathways identified in this research project may lead to new strategies for the treatment and/or prevention of mammary cancers in cats.