Genomic-guided precision oncology in canine cancer: from comparative genomics to liquid biopsy and molecular monitoring.

importanceTraditional cancer diagnostics in veterinary medicine are limited by invasiveness and insufficient sensitivity for real-time molecular monitoring. This review critically evaluates the clinical applicability of somatic mutation profiling and liquid biopsy technologies to establish an evidence-based, tiered framework for precision oncology in canine patients, with emphasis on veterinary-specific constraints and technology selection. OBSERVATIONS: Key somatic biomarkers demonstrate strong clinical utility: BRAF V595E achieves > 80% diagnostic sensitivity in canine urothelial carcinoma and is detectable non-invasively in urine via droplet digital polymerase chain reaction (ddPCR). The multicenter cancer detection in dogs (CANDiD) study demonstrated circulating tumor DNA-based liquid biopsy achieves 54.7% overall sensitivity and 98.5% specificity, though stage I detection remains critically limited at 16.1%, underscoring the current gap for early-stage screening. Minimal residual disease assessment via allele-specific oligonucleotide-PCR and next-generation sequencing enables detection of molecular relapse 42-168 days before clinical manifestation in canine lymphoma. However, analytical variability across platforms, lack of standardized pipelines, and high cost represent significant barriers to routine veterinary application. CONCLUSIONS AND RELEVANCE: Genomic-guided oncology offers substantial clinical value for canine cancer management yet requires veterinary-specific validation before broad adoption. Targeted sequencing panels currently represent the optimal balance of cost-effectiveness and clinical utility for most veterinary practitioners, while ddPCR is preferred for longitudinal tracking of known mutations. Liquid biopsy cannot serve as a standalone screening tool at present, but functions as a valuable complementary monitoring approach. Continued canine-specific biomarker research and multicenter data sharing are essential prerequisites for integrating precision medicine into routine veterinary care.