2510: Identification of Novel Synthetic Lethal Partners to Optimize PI3K Targeted Therapies in Canine Hemangiosarcoma

Grant Status: Open

Grant Amount: $168,857
Cheryl A. London, DVM PhD; Tufts Medical Center
March 1, 2018 - February 28, 2021
Sponsor(s): American German Shepherd Dog Charitable Foundation, Dachshund Club of America, Inc., Irish Setter Club of America Foundation, Inc., Scottish Terrier Club of America Health Trust Fund, Vizsla Club of America Welfare Foundation
Breed(s): -All Dogs
Research Program Area: Oncology - Hemangiosarcoma

Abstract

Hemangiosarcoma (HSA) is a cancer of the cells lining the blood vessels that is very aggressive and has nearly always spread by the time it is diagnosed. HSA accounts for 5-7% of all cancers in dogs resulting in approximately 25,000-50,000 new cases per year. The treatment of choice is surgical removal followed by chemotherapy administration. Unfortunately, despite aggressive therapy, the majority of dogs diagnosed succumb to their disease within 6-8 months. Virtually no improvements in outcome for affected dogs have occurred in the past 30 years despite multiple clinical trials and research efforts. More recently a new therapy has been developed targeting two receptors on HSA cells. However, the majority of dogs still died, by 10-12 months after treatment. The molecular pathway known as the PI3K/AKT/mTOR pathway has previously been implicated in the pathogenesis of many forms of cancer including HSA. Indeed, inhibitors of PI3K/AKT/mTOR pathway have some activity against HSA cell lines in the laboratory. The investigators have generated data showing that a subset of canine HSA tumors possess genetic mutations in PI3K that are known to activate the pathway in cancer cells.  In this study, they will fully characterize the expression and function of PI3K in canine HSA tumor cell lines and tumor samples. This information will then be leveraged to identify new ways to block the PI3K/AKT/mTOR pathway using a combination of small molecule inhibitors that are most effective at killing tumor cells. These data will then be used to design future clinical trials in dogs with HSA.

Publication(s)

None at this time.

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