01178-A: Radiosensitization of Canine Osteosarcoma with Rapamycin

Grant Status: Closed

Grant Amount: $12,952.47
Dr. Michael S. Kent, DVM, University of California, Davis
July 1, 2008 - March 31, 2009
Sponsor(s): Akita Club of America, Inc., American Boxer Charitable Foundation, Flat-Coated Retriever Foundation, German Wirehaired Pointer Club of America, Golden Retriever Foundation, Great Dane Club of America, Great Dane Club of America Charitable Trust, Great Pyrenees Club of Puget Sound, Greyhound Club of America, Irish Setter Club of America Foundation, Irish Wolfhound Association of the West Coast, Irish Wolfhound Club of America, Inc., Jeffrey Pepper, Leonberger Health Foundation, Mastiff Club of America, Rhodesian Ridgeback Club of the United States, Rottweiler Health Foundation, Saluki Health Research, Inc., Starlight Fund
Breed(s): -All Dogs
Research Program Area: Treatment

Project Summary

Osteosarcoma in the dog is a highly aggressive cancer that is often fatal. Management of this disease involves controlling the local tumor as well as its regional and distant metastasis. Despite aggressive therapy with radiation therapy, surgery and chemotherapy, median survival is about one year. The AKT/mTOR pathway is constitutively active in many forms of human cancer. We have found that this pathway is also activated in canine osteosarcoma. We have also shown that this pathway can be blocked using the drug rapamycin. Several studies in human cancer cell lines have shown that rapamycin can increase the radiosensitivity of in vitro. The goals of this study were to test the effect that the combinations of rapamycin and radiation have on cellular proliferation, clonogenicity and cell cycle kinetics in canine osteosarcoma. Results suggest that treatment intensification by a 2-week interradiation treatment interval coupled with interradiation chemotherapy is an effective treatment for dogs.

Publication(s)

Lurie DM, Gordon IK, Th�on AP, Rodriguez CO, Suter SE, Kent MS. (2009) "Sequential low-dose rate half-body irradiation and chemotherapy for the treatment of canine multicentric lymphoma." J Vet Intern Med. 23(5):1064-70. Lurie DM, Kent MS, Fry MM, Th�on AP. (2008) "A toxicity study of low-dose rate half-body irradiation and chemotherapy in dogs with lymphoma." Vet Comp Oncol.; 6(4):257-67.

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