ReviewVeterinary oncology: Biology, big data and precision medicine
Introduction
According to the data from Cancer Research UK (CRUK, 2012), there were 14.1 million new human cancer diagnoses worldwide and 8.2 million deaths.1 Reducing cancer mortality is clearly an international priority. However, despite incremental improvements in cancer therapies, the disease remains one of high morbidity and mortality causes in all species (Argyle and Blacking, 2008). Improvements in public health and the control of infectious diseases have compounded the problem making cancer the world's leading cause of death in humans. In addition, cancer has a huge impact on the economy through loss of productivity, loss of years of life, and cost related to treatment. According to the American Cancer Society, the total economic impact of premature death and disability from cancer worldwide was $895 billion2 in 2008.3 This figure represents 1.5% of world's GDP and does not include direct cost of treating cancer. According to Murphy and Topel (2003), a 10% reduction in cancer deaths worldwide would be worth $4.7 trillion in social value.
Cancer in veterinary species can have two broad consequences. In livestock species cancer can have a major economic impact, especially those with an infectious cause such as Marek's disease in poultry, or bovine leukosis in cattle, causing significant loss of production. In contrast, the major impact on companion animals relates to their long-term health and their relationship with their owners. Although true epidemiological data worldwide are lacking in veterinary medicine, we estimate that the incidence of cancer in dogs is around 1 in 3 (and 1 in 4–5 in cats) (Pang and Argyle, 2009). This is similar to a man and with a similar pattern of improved control of infectious diseases pushing cancer up the league table of significant causes of death.
Cancer treatments (and consequently cancer treatment centres) have increased significantly in the last 20 years. They have become the ‘accepted clinical practice’ and owners now have much broader access to facilities such as external beam radiation. The control of cancer and cancer treatment-related side effects is much improved with the development of new drugs (e.g. NK-1 inhibitors for nausea) and we have seen the first targeted drugs for veterinary oncology being approved and launched (see, for example, London et al., 2009).
We have also learnt a great deal about the biology of cancer in dogs and cats in the last two decades. This has been supported by the publications of species genomes which has also created, in small part, the tool box required to understand this disease at the genetic level and also to investigate the clear breed predispositions for certain types of cancer (Ostrander and Kruglyak, 2000). However, as with human medicine, we still recognize cancer as the leading chronic disease and one of the biggest causes of death in companion animals (Argyle and Blacking, 2008).
Section snippets
The hallmarks of cancer
It is very difficult to define what a cancer is and to put that definition into a clinical context. If one considers that homeostasis is fundamental to health, then cancer can be considered in terms of a breakdown in the homeostatic mechanisms that control cell growth, cell division and cell death. Consequently, we have to deal clinically with a group of cells that have lost control of intrinsic cell growth and division, and can, under certain circumstances, spread (metastasize) to distant
Challenging the traditional model of cancer development
In the last 10 years we have seen significant challenges to the traditional stochastic model of cancer development (described above). In many ways the simple model from initiation to metastatic cell (requiring the acquisition of multiple hits over time) did not fit well with our understanding of tissue and cell turnover in organ systems. An evolving model (cancer stem cell model) treats the cancer as an ‘organ system’ where the bulk tumour population is driven by a small number of cancer stem
Genes, dreams and cancer signatures
From a position over 20 years ago, when we could only look at single pathways or genetic changes in cancer cells in a stepwise fashion, we have moved to a position when we can examine thousands of genes in a cancer sample using gene array ‘chips’. Initially, these were expensive technologies but the cost has plummeted in recent years, accompanied by newer technologies such as high throughput sequencing and RNA sequencing (RNA-seq). RNA-seq uses Next Generation Sequencing (NGS) to rapidly
Why no cure?
We have experienced an exponential growth in understanding of cancer biology in the past 25 years. However, although there has been some shift in survival times and improved mortality in humans, we have not seen the paradigm shift that the new cancer technologies promised. Pragmatically, this should not be a surprise considering the complexity of the disease, but it is worth considering a number of issues that have arisen and how these may be overcome:
A cause for optimism?
Our ability to dissect the cancer genome and all of its components has far exceeded our ability to analyse and understand the data. We can therefore conclude that the complexity of the cancer cell is currently impeding our ability to define and produce better treatments and better outcomes for patients. As a community involved in cancer research or clinical oncology or both, what can we do to drive progress and is there a cause for optimism? The simple answer is that there is a great deal that
Conclusions
Despite a rather challenging view of cancer research and clinical oncology where complexity of this disease will constantly hinder progress, many of the hurdles described can be overcome to the benefit of all species. As a community, it is essential to think far beyond the translation of basic biology into clinical practice, and consider the defining research and application that will truly transform clinical practice to the benefit of patients. We have to remove the boundaries to research
Conflict of interest statement
Neither of the authors of this paper has a financial or personal relationship with other people or organizations that could inappropriately influence or bias the content of the paper.
Acknowledgements
The authors' work is currently and has been generously funded by the Petplan Charitable Trust, The RCVS Trust (now RCVS Knowledge), The Wellcome Trust, The BBSRC, the EPSRC and Dogs Trust.
David Argyle is in grateful receipt of an International Canine Health Award (made possible by a grant from Vernon and Shirley Hill) from the Kennel Club Charitable Trust to extend his research on canine cancer.
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Joint-winner of the Kennel Club Charitable Trust's International Award 2015.