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

Abstract

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.

Keywords: canine (dog); comparative oncology; immunotherapy; osteosarcoma; sarcoma.

Figure 1

Sustaining and bolstering existing comparative oncology research infrastructure for continued acceleration of sarcoma therapeutic discovery and translation to clinical trial evaluation. Increasing comparative oncology research funding and industry investment in development of species-specific molecular tools, paired with veterinary and medical collaborative sarcoma research, will enhance an already effective pathway for more predictive vetting of novel preclinical agents and movement into human clinical trials. Evaluation of small molecule immunotherapies, novel molecular-targeted agents, monoclonal/bi-specific antibodies, and adoptive cell therapies alone and in combination are likely to be especially informative to the field. Created with BioRender.com.

Figure 2

Integrating canine sarcoma trials in human oncology drug development. Considerations for the various types of clinical and biological data that can be generated through trials in dogs with spontaneous sarcoma and where in the human clinical trial pipeline integration of these data may be informative. Created with BioRender.com.