Molecular targets for anticancer therapies in companion animals and humans: what can we learn from each other?

Abstract

Despite clinical successes in the treatment of some early stage cancers, it is undeniable that novel and innovative approaches are needed to aid in the fight against cancer. Targeted therapies offer the desirable feature of tumor specificity while sparing healthy tissues, thereby minimizing side effects. However, the success rate of translation of these therapies from the preclinical setting to the clinic is dramatically low, highlighting an important point of necessary improvement in the drug development process in the oncology field. The practice of a comparative oncology approach can address some of the current issues, by introducing companion animals with spontaneous tumors in the linear drug development programs. In this way, animals from the veterinary clinic get access to novel/innovative therapies, otherwise inaccessible, while generating robust data to aid therapy refinement and increase translational success. In this review, we present an overview of targetable membrane proteins expressed in the most well-characterized canine and feline solid cancers, greatly resembling the counterpart human malignancies. We identified particular areas in which a closer collaboration between the human and veterinary clinic would benefit both human and veterinary patients. Considerations and challenges to implement comparative oncology in the development of anticancer targeted therapies are also discussed.

Characterization of P‐glycoprotein orthologs from human, sheep, pig, dog, and cat

“…Additionally, while we assessed effects of digoxin here, there are many other drugs that have narrow therapeutic indices, including anticancer drugs like busulfan and immunosuppressants such as tacrolimus (Basak et al, 2021; Chatelut et al, 2003; Paci et al, 2014). With domestic animals increasingly being treated for cancers, there will be a greater need to evaluate the safety of drugs traditionally used in humans in a species‐specific manner (Beltrán Hernández et al, 2021). Indeed, P‐gp‐mediated DDIs have been reported in veterinary animals that have led to chemotherapeutic drug toxicity (Mealey & Fidel, 2015).…”

A Comparative View on Molecular Alterations and Potential Therapeutic Strategies for Canine Oral Melanoma

“…Cancer is a leading cause of death in dogs [17], so could we benefit from joining forces with our human medic counterparts in a "One Health" approach? Perhaps reflecting common physiology, lifestyle, and environmental exposure to carcinogens, the range of spontaneously occurring tumours in dogs and humans display striking similarities, and these tumours arise and evolve in the presence of an intact immune system [18,19]. Much more is known about the molecular pathogenesis of human cancers, and this provides veterinary medicine with candidate factors for targeted investigation.…”

High Drug Resistance in Feline Mammary Carcinoma Cell Line (FMCm) and Comparison with Human Breast Cancer Cell Line (MCF-7)

“…In female cats, mammary cancer is the third most common neoplasia. 85–90% of these pathologies present a malignant phenotype, having extremely high mortality rates and a mean survival time of about one year [ 1 , 2 ]. Besides local recurrence, metastatic disease is also commonly observed, mainly involving regional lymph nodes, lungs, pleura, and liver [ 3 ].…”