engleski

“ONE HEALTH” APPROACH IN TUMOUR RESEARCH

Today cancer is one of the most prevalent diseases, and not just in humans. In the USA, it is estimated that approximately 500 new cases of cancer are diagnosed per 100, 000 of the population each year, whereas in dogs the estimate is 5, 300 cancer diagnoses per 100, 000 population. Comparative oncology is a quickly expanding field that examines both cancer risk and tumour development across species. Characterised by interdisciplinary collaboration, its goal is advancement of both human and animal health. Research in this area is mostly focused on finding an ideal animal model to study human cancer. This model should possess comparable histopathological features, biological behaviour and molecular and genetic characteristics.Considering the failures in cancer drug development and the complexity of cancer biology, the laboratory models of cancer suffer from some serious limitations. Experimental therapies tested in murine models have, all too often, elicited responses that only poorly predict the outcomes of those therapies being translated to the human setting. Murine bone marrow is generally less sensitive to the toxicity induced by chemotherapy than human bone marrow, suggesting that mice are not suitable for use in the evaluation of the adverse effects of novel chemotherapies. Also, genetically modified mice, transplantation and xenograft models obtained from the patient have shown that they do not mimic exactly the specificity of human cancer, thereby limiting their reliability to translational applications. In addition, one of the main disadvantages is the limited life-span of mice, which does not allow several fundamental features of the nature of human cancers to be reproduced: growth over long periods of time, genomic instability and tumour heterogeneity. Finally, there are discrepancies between the immune systems of mice and humans, which raises the question of using mouse models for a rigorous assessment of immunotherapy strategies. Tumour-bearing dogs capture the “essence” of the problem of cancer in a way that is not achievable with other animal models. In 2005, the canine genome was completely sequenced and a high degree of sequence similarity compared to human genome was identified. Canine cancers also share evolutionarily conserved genomic changes that are found in their human counterparts. Tumour initiation and progression processes in both humans and dogs are influenced by the same factors, including age, nutrition, sex and environment. They drink the water that we drink, sometimes eat the same food that we eat, they are exposed to the same air as we are and could, therefore, be considered epidemiological or aetiological sentinels of the disease. Pet tumours grow slowly in an intact immune system, allowing immune and cancer cells to interact for a long period of time, shaping each other, as well as showing the intratumour heterogeneity and genetic instability that is typical of human lesions. The histological and clinical presentation of numerous canine cancers closely parallels that of the corresponding cancers in humans. Yet, humans are not the only ones that benefit from the research of cancer. Biological similarities between canine and human cancers have also provided significant rationale for the study of novel therapeutic approaches in dogs. Furthermore, studying naturally occurring tumours in dogs has an ethical benefit, reducing the number of laboratory animals in which cancer is induced. In recent years, several groups of researchers have performed veterinary studies in order to test innovative strategies in a highly translational setting. These studies included a wide range of comparative tumours, such as lymphomas, melanomas, osteosarcomas, mammary gland tumours and brain tumours. The most active areas of research are the assessment of changes to genome architecture aimed at identifying regions of genome aberration shared between canine and human cancers (suggestive of a conversed mechanism of pathogenesis), comparative aspects of microRNA expression in canine and human cancers and the investigation of innovative therapeutic approaches with a high translational power for human and canine patients. Most recently, our faithful companions are used in the research of human tumours in a different manner, not only as a model. They are used in the context of tumour diagnostics, where a few studies have shown that human tumour diagnosis harnessing the superior canine olfactory ability is a promising alternative for the diagnostics of certain types of cancer. Besides dogs, there are other animals (both prone and resistant to cancer development) that offer their own unique opportunity to better understand the processes involved in tumourigenesis. Among them are marine mammals, bats, naked mole-rats, bowhead whales and elephants. As we can notice, the comparative oncology truly embraces all cancer risks with the goal to broaden our knowledge about tumours and translate this towards improving the health of humans and animals.

one health, tumor, animal

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