Synopsis

LeBlanc

Osteosarcoma (OS) is the most common malignant bone tumor in children. Despite efforts to develop and implement new therapies, patient outcomes have not measurably improved since the 1980s. Metastasis continues to be the main source of patient morbidity and mortality, with 30% of patients developing metastatic disease within 5 years of diagnosis. Research models are critical in the advancement of cancer research and include a variety of species including the mouse, zebrafish, and dog. Advancement in the field of OS research requires continued development and appropriate utilization of animal models.

A growing recognition of naturally occurring cancers in companion species has led to new insights into how veterinary patients can contribute to studies of cancer biology and drug development. In this presentation, animal models of OS are described, with specific examples and with a focus on the mouse and tumor-bearing pet dog as parallel and complementary models of human OS. Histologic, genomic, and clinical similarities known to exist between canine and human OS have supported the ongoing characterization of the dog as a potential model of pediatric and adolescent OS. Several advantages in rodent models—for example, homogeneity and rapid tumor engraftment and growth—are not reflective of what occurs in the human cancer patient. Pet dogs with OS represent a heterogenous group of patients, more accurately representing outbred human patient populations. OS in dogs develops spontaneously, but also in the context of an intact immune system and complex tumor microenvironment, both of which are increasingly recognized as important facets of the disease. This presentation will also provide an overview of the COP’s recent initiative to characterize canine OS using a variety of ‘-omic’ platforms and integrate this with available human OS datasets.

In addition to basic research carried out in the COP laboratory, clinical trials in pet dogs with OS conducted through the Comparative Oncology Trials Consortium (COTC) offer valuable scientific and clinical insight. In general, canine OS trials fall into one of four major categories: cancer biology, drug development, diagnostics, and imaging. Trials may also be designed to answer important questions in multiple categories. Comparative oncology trials can be structured to mirror their pediatric counterparts or designed to answer a veterinary-specific question or goal. Data generated from such trials can be used to advance a diagnostic or therapeutic procedure to directly benefit dogs, humans, or both species, if the hypothesis and generated dataset have translational relevance.