Targeting the Cell Cycle and Autophagy Reciprocal Communication Pathways in Sarcoma
Principal Investigator: Erin Dickerson, PhD
Project summary: Sarcomas are tumors of connective tissue that can arise anywhere in the body. They are often challenging to treat because they are extremely rare, preventing the development of beneficial therapies. Angiosarcomas are a type of sarcoma that arise from blood vessel forming cells, and most patients will die within three years of their diagnosis. While these tumors occur in fewer than 300 people each year in the US, a similar tumor, known as hemangiosarcoma, occurs commonly in dogs.
Our research has shown that studying this disease in dogs can help us better understand and potentially treat them in people. Using tumors from dogs being treated with the beta blocker propranolol and the chemotherapy doxorubicin, we compared gene signatures from dogs that showed long-term survival in response to this therapy to dogs that exhibited short-term survival.
Our data showed that dogs surviving more than one year had a specific signature that could be targeted by propranolol. Dogs that did not survive, also contained a very specific signature, and we identified a separate drug that can target these tumors. Our goal is to determine if these two drugs, propranolol and palbociclib, work better together to kill sarcomas. Because similar responses to propranolol have been observed in human angiosarcoma, our findings are likely to translate to human patients. The information obtained from this project will support grant applications to the NIH, DOD, and other agencies. Successful results will help us to refine our approach and guide the development of other treatment combinations.