Metabolic Alterations in Canine Mammary Tumors

SIMPLE SUMMARY: Cancer cells usually have a short timeframe for proliferation, which favors tumor growth. Therefore, they require more energy and intermediates to sustain biosynthetic pathways that will supply all the requirements for cell division. This event is known as metabolic reprogramming and is described in all cancer types, it also being a vulnerability for therapy. However, metabolic alterations in canine mammary tumors are poorly explored. In this review, we compile the metabolic rewiring described in canine mammary tumors, which could be used as a therapeutic opportunity for treatment in veterinary oncology. ABSTRACT: Canine mammary tumors (CMTs) are among the most common diseases in female dogs and share similarities with human breast cancer, which makes these animals a model for comparative oncology studies. In these tumors, metabolic reprogramming is known as a hallmark of carcinogenesis whereby cells undergo adjustments to meet the high bioenergetic and biosynthetic demands of rapidly proliferating cells. However, such alterations are also vulnerabilities that may serve as a therapeutic strategy, which has mostly been tested in human clinical trials but is poorly explored in CMTs. In this dedicated review, we compiled the metabolic changes described for CMTs, emphasizing the metabolism of carbohydrates, amino acids, lipids, and mitochondrial functions. We observed key factors associated with the presence and aggressiveness of CMTs, such as an increase in glucose uptake followed by enhanced anaerobic glycolysis via the upregulation of glycolytic enzymes, changes in glutamine catabolism due to the overexpression of glutaminases, increased fatty acid oxidation, and distinct effects depending on lipid saturation, in addition to mitochondrial DNA, which is a hotspot for mutations. Therefore, more attention should be paid to this topic given that targeting metabolic fragilities could improve the outcome of CMTs.