Abstract A066: Could ancestry play a role in cancer development? Insights from a risk assessment and early detection test of naturally occurring cancers in companion dogs

Abstract Companion dogs have a lifetime cancer risk similar to that of humans. This excess risk, as compared to what is seen in other species, seems to be due to our recent success in outliving our evolutionarily adapted lifespan. For cancers to develop, a cancer-permissive environment must be present, which may exist months or even years before a tumor becomes detectable. We have developed the Shine On Suspicion (SOS) test; a flow cytometry based test to detect these changes that lead to a cancer-permissive environment. To make this test actionable, we combined it with eBAT, a novel bispecific ligand-targeted toxin that targets emerging cancer cells and the inflammatory niche to disrupt cancer formation. The Shine On Study used machine- learning algorithms to determine cancer risk based on a training set of 97 dogs with known conditions and a test set of 209 adult dogs with no evidence of cancer or other chronic diseases. Dogs assigned to the low-risk category had a less than 4% chance of developing cancer within 400 days after testing, whereas dogs assigned to the high-risk category had a nearly 25% chance of developing cancer in that timeframe. By 1,450 days, more than 50% of dogs assigned to the high-risk category developed cancer. Surprisingly, the SOS test’s specificity varied by breed. In Boxers and Portuguese Water Dogs the test accurately predicted the risk of hemangiosarcoma and other malignancies, whereas for Golden Retrievers, the test accurately predicted the risk for hemangiosarcoma, but no significant difference in the development of other cancers was observed between high-risk and low-risk groups. This suggests that the contribution of the cancer-permissive environment detected by the SOS test interacts with heritable factors, i.e., those defined by ancestry in creating the overall cancer risk state. To date, eBAT interception has been administered to 9 dogs, with only 1 potentially developing cancer 2 years after treatment. The drug is well-tolerated and shows promising outcomes. Future research aims to refine the SOS test, understand breed-specific responses, and explore the identity and function of niche- forming cells to improve cancer prevention strategies and their applicability to humans. Citation Format: Ashley J Schulte, Taylor A DePauw, Ali Khammanivong, Mitzi Lewellen, Lauren Burt, Rose Dicovitsky, Amber L Winter, Kathleen M Stuebner, Andrea Chehadeh, Sara Pracht, Christopher Ober, Kari L Anderson, Esther Nell, Antonella Borgatti, Michael S Henson, Erin B Dickerson, Aaron L Sarver, Daniel A Vallera, Gary R Cutter, Jaime F Modiano. Could ancestry play a role in cancer development? Insights from a risk assessment and early detection test of naturally occurring cancers in companion dogs [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A066.