Feline oral squamous cell carcinoma (FOSCC) is one of the most treatment-refractory cancers in veterinary medicine and carries universally grave prognosis after even aggressive, multimodal treatment, most commonly due to local tumor regrowth. Even though its clinical outcome is frustratingly poor, little is known about its background radiation/cancer biological mechanisms. Recently, our group discovered thatFOSCC expresses a protein named Bmi-1. This protein is involved in cell biology mechanisms including self renewal, which gives the cell stem-cell characteristics and therefore, cancer cells with those characteristics are called “cancer stem cells”. Different types of human cancers are also known to express Bmi-1 and in some cancers high expression of Bmi-1 was shown to be a negative prognostic factor. A novel chemical, called PTC-209, has been shown to possess strong anti-Bmi-1 activity in multiple human cancers. Our group have discovered that PTC-209 strongly inhibits proliferation of FOSCC cells. Therefore, to further assess PTC-209’s therapeutic potential against FOSCC, we propose to assess (1) if subset of FOSCC cells that express Bmi-1 protein possessmore “stem cell” like property that may make this cancer more refractory to treatment insults, (2) if those cells are more resistant to radiation therapy, (3) if those stem-like cancer cells become more effectively killed if radiation therapy and PTC-209 treatments are combined, and (4) if PTC-209 can alter other characteristics of FOSCC stem cells; local invasiveness of the cancer cells.