What can our canine friends tell us about cancer?

Comparative oncology is a field of study within cancer that has been adopted to study cancer and develop new therapies. It involves studying cancer in animals to uncover similarities between human and animal cancers. By combining scientific findings across a range of species, including companion animals such as dogs and horses or non-human primates such as monkeys, comparative oncology will advance cancer research and help develop effective novel therapies. This approach not only explores cancers in both animals and humans but also aims to bridge the gap between human and veterinary medicine. By examining similarities and differences in cancer biology, progression and treatment responses across species, comparative oncology provides valuable insights that can benefit both fields. Understanding how cancer behaves in animals can offer new perspectives and potential therapies for human patients. Conversely, while findings in human oncology can inform veterinary medicine, leading to improved diagnostics and treatments for animals. (Figure 1 summarises the aims of comparative oncology). This article aims to explore this field of oncology further by discussing what it entails, the methodologies utilised, some recent advancements, and finally, things to look out for in the future.

Comparative oncology has been developed and expanded into two areas of study. This includes spontaneous oncology and experimental oncology. Spontaneous oncology focuses on naturally occurring tumours in animals by investigating aspects of carcinogenesis, epidemiology, diagnosis, and treatment. It provides unique insights by drawing comparisons with human oncology research. These results can then be extrapolated to human oncology to gain a better understanding of cancer. This is because the similarities and differences observed in naturally occurring tumours across species provide valuable insights into underlying mechanisms within tumours and treatment responses. Experimental oncology serves as a distinct discipline where there are specialisations such as studying viral, chemical, and radiation oncogenesis alongside studying environmental factors such as pollution residues and food additives. This area involves studying both spontaneous tumours in animals and lab settings, where controlled conditions are used to explore different parts of cancer biology and treatment strategies.

Additionally, the primary methodology utilised in comparative oncology involves studying spontaneous tumours in animals. Unlike artificially induced tumours in lab animals, these spontaneous tumours in pets closely mimic the complexity and heterogeneity of human cancers. For example, canines will live in similar living environments and experience similar external stimuli to their owner, such as pollution. The nature of these external stimuli means that they develop cancer in similar ways caused by epigenetic alterations, metabolic, and immune changes. (Figure 2 illustrates this process). Furthermore, comparative oncology uses advanced imaging techniques, genetic analysis, and immunological studies to predict pathways that may be shared among animals and humans which, could drive cancer development. Overall, these methods will allow the identification of promising therapies which directly target cancer and expand on current treatment choices such as chemotherapy and immunotherapy. 

One of the recent advancements in comparative oncology relates to osteosarcomas. This refers to cancer cells which begin to grow in the bones. For this specific form of cancer, molecular signatures were identified to predict clinical outcomes for both humans and canines, which can help improve treatment outcomes. Led by Amy K. LeBlanc, scientists have identified gene activity patterns in osteosarcoma tumours in nearly 200 dogs, revealing distinct groups with varying prognoses. These findings help us understand the biology behind osteosarcomas further and can potentially help us develop targeted therapies that take advantage of the immune system to treat the disease in both species. This potentially includes a range of therapies including PD-L1 inhibitors and cancer vaccines targeting the immune system. Moreover, breakthroughs in immunotherapies such as checkpoint inhibitors and CAR-T cell therapy are effective in treating haematological malignancies in both humans and canines. Furthermore, studies in canine melanoma reveal similar gene expression changes to human melanoma, such as in the PI3K/AKT/mTOR and MAPK pathways, even when the driver mutations are different. (Figure 3 shows how the pathway contributes to cancer). Useful data was provided in trials using companion animals with spontaneous tumours, providing an insight into safety, dosage, and efficacy, which have paved the way to develop treatments for both species. 

To conclude, it is clear with comparative oncology, researchers will be able to identify new molecular targets, assess novel drugs, and identify patient populations which will benefit the most from these therapies. It holds great promise in helping streamline cancer diagnosis further and even plays a role in preventing cancer. While the field shows great potential, more studies still need to be conducted to understand the similarities and differences in cancers between animals and humans. Additionally, more collaboration is needed amongst oncologists, veterinarians, and researchers across these disciplines to harness collective expertise to address questions relating to cancer diagnosis, treatment, and prevention. Ultimately, this field will help us identify new avenues of treating and diagnosing cancer whilst improving healthcare outcomes for humans and animals alike. 

Written by Harene Elayathamby

Related article: Rare zoonotic diseases

REFERENCES

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Mochel, J.P. et al. (2018) Car T-cell immunotherapy in human and veterinary oncology: Changing the odds against hematological malignancies [Preprint]. doi:10.20944/preprints201811.0525.v1. 

LeBlanc AK, Mazcko CN, Khanna C. (2016) ‘Defining the Value of a Comparative Approach to Cancer Drug Development’, Clinical cancer research : an official journal of the American Association for Cancer Research, 22(9). p. 2133-2138. doi: 10.1158/1078-0432.CCR-15-2347

FIGURE REFERENCES

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