Targeting Metabolism and Mast Cell Modulation in Canine TCC: A Literature Review with Translational Implications

Transitional cell carcinoma (TCC) in dogs presents a unique oncologic challenge due to its aggressive nature, metabolic adaptability, and frequent resistance to therapies. However, its metabolic and immune interactions extend beyond oncology, providing a model for human disease. This paper examines the metabolic foundations of canine TCC, emphasizing oxidative stress, mast cell interactions, and glycolytic flexibility—key pathways associated with neuroinflammation and mast cell disorders. We propose a multi-modal therapeutic approach that targets tumor escape mechanisms but provides insights into mast cell and autonomic nervous system communication, which plays a role in chronic inflammatory and neurodegenerative diseases, including interstitial cystitis and endometriosis. These findings provide a link between oncology, immunology, and autonomic dysfunction. This review was developed with consideration for veterinary oncology teams, including potential applications at the UW Madison Veterinary Hospital.Keywords: Canine transitional cell carcinoma; Metabolic targeting; Mast cell modulation; Oxidative stress; Glutathione; Autonomic dysfunction; Bladder cancer; Interstitial cystitis