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MT05-010: Expression and Pharmacologic Inhibition of Anti-Apoptotic BCL-2 Family Members in Feline Vaccine-Associated Sarcoma and Oral Squamous Cell Carcinoma

Vaccine-associated sarcoma (VAS) and oral squamous cell carcinoma (OSCC) are two of the most common and troubling feline neoplasms encountered in veterinary practice. A better understanding of the biology of these diseases is necessary to facilitate the discovery of novel efficacious therapies. Anti-apoptotic proteins such as those in the Bcl-2 family are commonly expressed in neoplasia, and their pharmacologic inhibition may be an important novel treatment modality for veterinary cancers. The hypothesis we intend to test is that anti-apoptotic Bcl-2 family members will be detectable in feline VAS and OSCC, and their pharmacologic inhibition with the small molecule ABT-737 will result in significant potentiation of chemosensitivity in vitro and in vivo. This hypothesis will be tested by the completion of the following specific aims: 1) Determine the expression of Bcl-2, Bcl-XL and Bcl-w in a panel of feline VAS and OSCC cell lines and archived paraffin embedded tissues; 2) Determine the effect of ABT-737 on the growth and chemosensitivity of VAS and OSCC cells in vitro; 3) Determine the effect of ABT- 737 on the growth and chemosensitivity of VAS tumors in a murine xenograft. Successful identification of anti-apoptotic Bcl-2 family members and their pharmacologic inhibition with ABT-737 will provide important proof of principle and proof of target, justifying the clinical evaluation of Bcl-2 family inhibition in cats with VAS and OSCC.

Grant ID: MT05-010

Status: Active

Year Funded: 2005

Amount awarded: $22,700

Investigator: David M. Vail, Douglas H. Thamm, E.J. Ehrhart III; Colorado State University