Abstract PR008: Identification and characterization of the cancer permissive environment in companion dogs
Authors: Modiano Jaime F. , Schulte Ashley J. , DaPauw Taylor A. , Khammanivong Ali , Kim Jong H. , Sarver Aaron L. , Cutter Gary R. , Lindquist Eric , Makielski Kelly M. 
Published: January 2023

Abstract
Domestic dogs are the only species besides humans where we recognize spontaneous, non-transmissible cancers as a significant cause of mortality(1-3). Recently, there has been a recognition that an important aspect of the natural history of cancer is that both species “live longer than nature intended” thanks to social, medical, and technological advances. We and others have proposed that this extended longevity is partly responsible for a decline in cancer protective mechanisms, and possibly for the arisal of cancer permissive (aged) environments(1). We have developed platforms to study the development of these environments. One such platform is the Shine On Suspicion (SOS) test, which uses flow cytometry and machine learning to identify patterns of mesenchymal and progenitor cells in blood that are associated with the presence of cancer or with the increased risk of developing cancer. Our hypothesis is that the cells responsible for these patterns contribute to the formation and/or to the remodeling of the cancer niche. The training set for the Shine On project included a group of healthy dogs that were past puberty but had not reached the age boundary where cancer risk is apparent (2-4 years old), and three independent groups of dogs with pathologically confirmed (1) hemangiosarcomas, (2) other malignant cancers, or (3) benign splenic hematomas. The validation set included 209 dogs over 6 years of age that had no evidence of cancer or other chronic diseases. Our data show that using the SOS test, we could assign dogs to a “low-risk” category, where the probability of developing cancer over the next 400 days (approximately 1/10th of a modern domestic dog’s lifespan) was less than 4%, or to a “high-risk” category, where the probability of developing cancer over the same time period was almost 25%, and it increased to more than 50% by 1,450 days. Intriguingly, as we followed dogs assigned to the low-risk category beyond 400 days, many converted to a high-risk category, with the relative risk of cancer in this group increasing in a fashion that was comparable to that seen in dogs originally assigned to the high-risk category. Ongoing experiments using the SOS test and other platforms seek to define the identity and the functional properties of the putative-niche forming cells, their relationship to biological aging, and the development of safe and effective interventions that can delay or prevent cancer in companion dogs – and eventually in humans. References: 1. A. L. Sarver, K. M. Makielski, T. A. DePauw, A. J. Schulte, J. F. Modiano, Increased risk of cancer in dogs and humans: a consequence of recent extension of lifespan beyond evolutionarily-determined limitations? Aging Cancer 3, 3-19 (2022). 2. L. Nunney, The real war on cancer: the evolutionary dynamics of cancer suppression. Evol Appl 6, 11-19 (2013). 3.S. M. Schwartz et al., Lifetime prevalence of malignant and benign tumours in companion dogs: Cross-sectional analysis of Dog Aging Project baseline survey. Vet Comp Oncol, (2022).
Citation Format: Jaime F. Modiano, Ashley J. Schulte, Taylor A. DaPauw, Ali Khammanivong, Jong H. Kim, Aaron L. Sarver, Gary R. Cutter, Eric Lindquist, Kelly M. Makielski. Identification and characterization of the cancer permissive environment in companion dogs [abstract]. In: Proceedings of the AACR Special Conference: Aging and Cancer; 2022 Nov 17-20; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_1):Abstract nr PR008.