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.

Keywords: companion animals; comparative oncology; molecular targets; targeted therapy.

Figure 1

Proposed approach for the development of anticancer targeted therapies. First, encouraging results are obtained in preclinical studies (e.g. rodents) for a targeted therapy utilizing a particular target. The therapy can be evaluated for the treatment of relevant cancers in companion animals expressing the target in question, allowing access to novel and promising therapeutic approaches for these veterinary patients. Robust data are thus acquired in a more relevant setting, to guide the translation of the therapy towards the equivalent human cancer while increasing translational success. At the same time, the use of current successful targeted therapies in the human clinic can be expanded to the veterinary clinic, based on the knowledge of which targets are present in the different canine and feline cancers.

Figure 2

Promising molecular targets for the development of anticancer targeted therapies in humans and companion animals. 1. Most advanced and utilized targets with high homology across species for the five most well-characterized cancer types: EGFR and HER2. Other very promising targets: FR, CXCR4, IGFR-1 and PDGFR. 2. Signal deregulation of these membrane proteins, mostly tyrosine kinase receptors, leads to cell proliferation, survival, migration and tumorigenesis. 3. Categories of therapies most often used to interfere with the targets extracellularly or intracellularly. EGFR: epidermal growth factor receptor; HER2: human epidermal growth factor receptor 2; PDGFR: platelet derived growth factor receptor; IGF-1R: insulin-like growth factor 1 receptor; FR: folate receptor; CXCR4: C-X-C chemokine receptor type 4. TKI: tyrosine kinase inhibitor.