Abstract 3914: Leveraging canine osteosarcoma as a model to advance precision medicine and targeted therapies in human osteosarcoma

Osteosarcoma (OS) is the third most prevalent tumor in adolescence, histologically characterized by the proliferation of abnormal osteoid-producing mesenchymal cells. Surgery remains the primary approach for OS treatment, but outcomes are poor without chemotherapy. Combining surgery, radiotherapy, and chemotherapy has improved results, yet 5-year survival rates persist at 60-70%. Despite advances in molecular medicine, progress in the treatment of OS has been limited, no significant breakthroughs have been achieved in systemic therapy, particularly for relapsed OS. Additionally, there is no consensus on the optimal treatment for these cases, leaving a substantial unmet need for effective therapies.Precision medicine trials (PMTs) have gained traction due to the ability to map the genomic profiles of individual tumors and match them to targeted therapies, but is still a challenge for OS due to limited efficacy and low enrollment rate. This low enrollment rate is due to several challenges, including tumor heterogeneity, limited molecular targets, and logistical in conducting trials. These barriers hinder the full realization of the potential benefits of PMTs to improve patient outcomes. One promising avenue is the use of naturally occurring canine OS, which share strong biological and molecular similarities with humans. Canine OS is estimated to be 10 times more common in pet dogs than in humans. Moreover, dogs develop these tumors spontaneously, with an intact immune system and comparable environmental exposures to humans, making them a valuable model for studying OS and improving the design of human trials. This study leverages data from 202 spontaneous canine OS, aiming to bridge the gap between preclinical investigations and clinical application. We utilized real-world clinical-genomic data from the FidoCure® platform, a canine precision medicine initiative that uses next-generation sequencing (NGS) to screen for cancer-associated genomic alterations. We identified that the most common genomic alterations occurred in tumor suppressor genes TP53, SETD2, PTPRJ, PTEN, RB1, DMD, BRCA1/2, and oncogene PIK3CA. These findings are consistent with the genomic profile seen in humans, reinforcing the value of the canine model. We also analyzed the correlation between small-molecule targeted therapies and genomic alterations. Through FidoCure®, veterinarians can leverage insights from the NGS panel to apply any of 11 human-approved therapies. Our analysis identified significant benefits from small-molecules when used as adjuvant treatment alongside chemotherapy with median survival of 354 days compared to 194 days when just chemotherapy is used (P=0.0011). Our study demonstrates the potential of combining small-molecule targeted therapies with traditional treatments, emphasizing the value of cross-species models in advancing osteosarcoma research and treatment. Citation Format: Lucas Rodrigues, Kevin Wu, Garrett Harvey, Gerald Post, Aubrey Miller, Lindsay Lambert, Christina Lopes, James Zou. Leveraging canine osteosarcoma as a model to advance precision medicine and targeted therapies in human osteosarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3914.