The NCI DOG2 Project Overview: Contributions to Osteosarcoma Research

The mission of the NCI Comparative Oncology Program (COP) is to utilize the canine cancer patient to better understand cancer biology and drug development to improve outcome for both dogs and humans. To advance this mission, the COP has taken a specific research focus in osteosarcoma, linking canine clinical trial activities to laboratory efforts focused on comparative tumor biology and genomics.

Osteosarcoma (OS) is an aggressive pediatric/adolescent/young adult malignancy and is the most common malignant bone tumor in this patient population. Similarly, canine OS is an aggressive, naturally-occurring bone tumor of dogs that is >10x more common than in humans. Patients with metastatic or relapsed disease have dismal outcomes, with survival rates less than 30% despite aggressive salvage regimens. Standard of care for canine OS patients consists of amputation of the affected limb to achieve local tumor control, followed by systemic platinum-based chemotherapy. However, many clinical studies, including our own clinical trials that include over 400 canine patients, demonstrate that development of metastases, most often to the lung, occur in over 90% of canine patients within several months of diagnosis. A comprehensive genomic framework of canine OS is needed to correlate the biologic and clinical facets of the disease in dogs, and to understand how they relate to what is known in human OS. To address this gap in knowledge, we have created the DOG² project (Decoding the Osteosarcoma Genome in Dogs (DOG²)). The goals of DOG² are to gain improve knowledge of comparative OS cancer biology to enhance dog to human translation, and to discover new drug targets and companion biomarkers in support of improved outcomes for humans. Establishing the genomic framework of naturally occurring OS in pet dogs will enable us to link knowledge gained through experimentally induced mouse models and clinical studies of human OS. Integrating mouse, dog and human data in this way has strong potential to improve the landscape of effective treatment options for OS. Armed with this knowledge, future clinical trials in pet dogs, conducted through the COP’s clinical trial infrastructure, can be rationally designed to test targeted strategies to combat OS disease progression. Such trials provide valuable insight into pharmacokinetic/pharmacodynamic relationships and drug efficacy, leading to more effective human clinical trials conducted by our pediatric oncology colleagues.