Abstract: Background: Osteosarcomas account for most primary bone malignancies in dogs. Despite aggressive conventional therapies, most dogs eventually succumb to this disease. A rapidly growing genomic understanding of canine osteosarcoma alongside an increasing arsenal of genomically guided therapeutic options for human cancers is now pointing to new potential therapeutic targets for canine osteosarcoma.
Hypothesis/Objectives: To uncover actionability horizons, our objective was to evaluate the genomic landscape of canine osteosarcoma and identify biomarkers with diagnostic, prognostic, and therapeutic associations.
Animals: Sixty-five canine osteosarcoma cases submitted for tumor genomic analysis with SearchLight DNA® were selected for evaluation.
Methods: Osteosarcoma samples profiled with SearchLight DNA®, a canine cancer gene sequencing panel, were included in this case series. Mutations with biomarker associations, including those associated with responses to targeted therapies based on canine or human cancer evidence, were identified and quantified.
Results: In 65 dogs with osteosarcoma, 754 (167 unique) mutations were identified in 79 genes, with TP53 being the most frequently mutated gene. Ten genes bore mutations with evidence supporting sensitivity to 4 FDA-approved targeted therapies, accounting for 46 patients (71%) for whom therapeutic biomarkers were associated with at least 1 FDA-approved targeted therapy. Three of these drugs are readily available to veterinarians from at least 1 major compounding pharmacy.
Conclusions and clinical importance: Understanding the genomic landscape of canine osteosarcoma in the context of mutation-based biomarker evidence supports the use of targeted therapies already available to veterinarians. These data also present opportunities to leverage human FDA-approved therapies in veterinary patients.
