Comparative Cancer Genetics and Veterinary Therapeutics in Dogs and Cats: A Species-Aware Framework for Comparative Oncology.

Cancer remains one of the leading causes of death worldwide, affecting not only humans but also companion animals such as dogs and cats. Although traditional rodent models have long served as the foundation of preclinical oncology research, their limited ability to replicate the complexity of spontaneous human cancers has driven interest in comparative oncology. Dogs and cats develop naturally occurring tumors that closely resemble human malignancies in histopathology, molecular alterations, tumor microenvironments, and treatment response. These species also share exposure to environmental carcinogens and demonstrate conserved pharmacokinetic and pharmacodynamic (PK/PD) profiles of several chemotherapeutic agents. This review provides a comprehensive comparison of cancer epidemiology, tumor biology, pharmacologic treatment modalities, drug formulation challenges, and regulatory considerations in humans, dogs, and cats. Key molecular targets such as TP53, HER2, EGFR, and PD-L1 exhibit cross-species conservation, supporting the relevance of companion animals in biomarker discovery and drug screening. However, interspecies differences in drug metabolism, enzyme expression (e.g., CYP450), and drug tolerability underscore the importance of species-specific dosing strategies and therapeutic drug monitoring. Advanced delivery platforms-including liposomes, nanoparticles, and antibody-drug conjugates-have also been successfully translated into veterinary oncology. Comparative analyses across humans and companion animals may inform biomarker prioritization, PK/PD modeling, and formulation design; however, species-specific differences require cautious interpretation and veterinary-centered dosing and safety considerations. Companion animals serve not only as valuable models for cancer research but also as direct beneficiaries of precision oncology. Future work should prioritize harmonized veterinary trial designs and improved cross-species data standards, with translational applications considered as a downstream benefit.