Naturally occurring canine sarcomas: Bridging the gap from mouse models to human patients through cross-disciplinary research partnerships.

Fueled by support from the National Cancer Institute's "Cancer Moonshot" program, the past few years have witnessed a renewed interest in the canine spontaneous cancer model as an invaluable resource in translational oncology research. Increasingly, there is awareness that pet dogs with cancer provide an accessible bridge to improving the efficiency of cancer drug discovery and clinical therapeutic development. Canine tumors share many biological, genetic, and histologic features with their human tumor counterparts, and most importantly, retain the complexities of naturally occurring drug resistance, metastasis, and tumor-host immune interactions, all of which are difficult to recapitulate in induced or genetically engineered murine tumor models. The utility of canine models has been particularly apparent in sarcoma research, where the increased incidence of sarcomas in dogs as compared to people has facilitated comparative research resulting in treatment advances benefitting both species. Although there is an increasing awareness of the advantages in using spontaneous canine sarcoma models for research, these models remain underutilized, in part due to a lack of more permanent institutional and cross-institutional infrastructure to support partnerships between veterinary and human clinician-scientists. In this review, we provide an updated overview of historical and current applications of spontaneously occurring canine tumor models in sarcoma research, with particular attention to knowledge gaps, limitations, and growth opportunities within these applications. Furthermore, we propose considerations for working within existing veterinary translational and comparative oncology research infrastructures to maximize the benefit of partnerships between veterinary and human biomedical researchers within and across institutions to improve the utility and application of spontaneous canine sarcomas in translational oncology research.

Role of Periostin Expression in Canine Osteosarcoma Biology and Clinical Outcome.

Periostin is a matricellular protein important in regulating bone, tooth, and cardiac development. In pathologic conditions, periostin drives allergic and fibrotic inflammatory diseases and is also overexpressed in certain cancers. Periostin signaling in tumors has been shown to promote angiogenesis, metastasis, and cancer stem cell survival in rodent models, and its overexpression is associated with poor prognosis in human glioblastoma. However, the role of periostin in regulating tumorigenesis of canine cancers has not been evaluated. Given its role in bone development, we sought to evaluate mRNA and protein expression of periostin in canine osteosarcoma (OS) and assess its association with patient outcome. We validated an anti-human periostin antibody cross-reactive to canine periostin via western blot and immunohistochemistry and evaluated periostin expression in microarray data from 49 primary canine OS tumors and 8 normal bone samples. Periostin mRNA was upregulated greater than 40-fold in canine OS tumors compared to normal bone and was significantly correlated with periostin protein expression based on quantitative image analysis. However, neither periostin mRNA nor protein expression were associated with time to metastasis in this cohort. Gene Set Enrichment Analysis demonstrated significant enhancement of pro-tumorigenic pathways including canonical WNT signaling, epithelial-mesenchymal transition, and angiogenesis in periostin-high tumors, while periostin-low tumors demonstrated evidence of heightened antitumor immune responses. Overall, these data identify a novel antibody that can be used as a tool for evaluation of periostin expression in dogs and suggest that investigation of Wnt pathway-targeted drugs in periostin overexpressing canine OS may be a potential therapeutic target.

The importance of preventative medicine in conjunction with modern day genetic studies.

Genetic screening in the primary care setting is the future of preventative medicine. Genetic testing is an important medical tool for assessing various inheritable diseases, conditions, and cancers. The ability to diagnose patients before symptoms surface can help lessen the severity of symptoms and promote quality of life. However, genetic screening can cause psychological distress from the knowledge of test results, in some cases only serving to increase the risk of developing a condition due to stress. Genetic testing can be conducted anytime in life, even before birth. In this review, a compilation of genetic testing's definitions and boundaries, factors influencing an individual's test outcomes, and an overview of a wide variety of diseases, conditions and cancers were collected.