Canine sarcomas as a surrogate for the human disease

Abstract

Pet dogs are becoming increasingly recognized as a population with the potential to inform medical research through their treatment for a variety of maladies by veterinary health professionals. This is the basis of the One Health initiative, supporting the idea of collaboration between human and animal health researchers and clinicians to study spontaneous disease processes and treatment in animals to inform human health. Cancer is a major health burden in pet dogs, accounting for approximately 30% of deaths across breeds. As such, pet dogs with cancer are becoming increasingly recognized as a resource for studying the pharmacology and therapeutic potential of anticancer drugs and therapies under development. This was recently highlighted by a National Academy of Medicine Workshop on Comparative Oncology that took place in mid-2015 (http://www.nap.edu/21830). One component of cancer burden in dogs is their significantly higher incidence of sarcomas as compared to humans. This increased incidence led to canine osteosarcoma being an important component in the development of surgical approaches for osteosarcoma in children. Included in this review of sarcomas in dogs is a description of the incidence, pathology, molecular characteristics and previous translational therapeutic studies associated with these tumors. An understanding of the patho-physiological and molecular characteristics of these naturally occurring canine sarcomas holds great promise for effective incorporation into drug development schemas, for evaluation of target modulation or other pharmacodynamic measures associated with therapeutic response. These data could serve to supplement other preclinical data and bolster clinical investigations in tumor types for which there is a paucity of human patients for clinical trials.

Keywords: Canine; Comparative oncology; Drug development; Hemangiosarcoma; Osteosarcoma; Sarcomas.

Fig. 1.

Correlation of Cancer Mortality to Standard Breed Height (A) and Weight (B) in North American Dogs. Frequency of death from cancer is from Fleming et al., 2011, and standard breed height and weight were compiled from breed information from the American Kennel Club (http://www.akc.org/dog-breeds). Correlation value (r) and significance (P) were calculated using a Spearman correlation test using GraphPad Prism v7.0a (GraphPad Software, Inc., La Jolla, CA).

Fig. 2.

Histological features of common canine sarcomas. (A) Malignant peripheral nerve sheath tumor demonstrating characteristic concentric whirling of spindle cells around central sclerotic collagen (asterisk). (B) Osteoblastic osteosarcoma with polygonal neoplastic osteoblasts producing and embedded within eosinophilic neoplastic bone matrix (arrowhead). (C) Histiocytic sarcoma, characterized by marked cellular pleomorphism, with multi-nucleate and karyomegalic cells, and bizarre mitotic figures (arrows). (D) Splenic hemangiosarcoma. Neoplastic cells are forming irregular, anastomosing, blood-filled vascular spaces. 20x magnification, H&E staining.