What Animal Cancers teach us about Human Biology

Abstract

Cancers in animals present a large, underutilized reservoir of biomedical information with critical implication for human oncology and medicine in general. Discussing two distinct areas of tumour biology in non-human hosts, we highlight the importance of these findings for our current understanding of cancer, before proposing a coordinated strategy to harvest biomedical information from non-human resources and translate it into a clinical setting. First, infectious cancers that can be transmitted as allografts between individual hosts, have been identified in four distinct, unrelated groups, dogs, Tasmanian devils, Syrian hamsters and, surprisingly, marine bivalves. These malignancies might hold the key to improving our understanding of the interaction between tumour cell and immune system and, thus, allow us to devise novel treatment strategies that enhance anti-cancer immunosurveillance, as well as suggesting more effective organ and stem cell transplantation strategies. The existence of these malignancies also highlights the need for increased scrutiny when considering the existence of infectious cancers in humans. Second, it has long been understood that no linear relationship exists between the number of cells within an organism and the cancer incidence rate. To resolve what is known as Peto's Paradox, additional anticancer strategies within different species have to be postulated. These naturally occurring idiosyncrasies to avoid carcinogenesis represent novel potential therapeutic strategies.

Keywords: Peto's paradox; anticancer mechanisms; infectious tumour; non-human malignancies; paediatric cancer; transmissible cancer.

Figure 1

A brief history of the universe, animal life and cancer. Shown here is a timeline highlighting the first verified occurrence/naming of novel features relating to cancer (blue), key developments in cancer sciences and oncology (red) and key medical and scientific uses of animals (green).

Figure 2

An unusual quartet of infectious cancer hosts. Infectious cancer whereby cancer cells can be transmitted between individuals has (so far) been identified in four different animal populations: (A) Dogs (Canis familiaris) can suffer from canine transmissible venereal sarcoma (CTVS), also known as canine transmissible venereal tumour (CTVT), transmissible venereal tumour (TVT), Sticker tumour, Sticker's Disease or infectious sarcoma. It is a rare disease in North and Central Europe and North America, where stray dog populations are tightly controlled . (B) Syrian (golden) hamsters (Mesocricetus auratus) in captivity have been to be affected by contagious reticulum cell sarcoma which apparently can be transmitted between individuals via either cannibalism or a mosquito vector , . Most of the work on this disease was done during a period of twenty years ending in the mid-1960s -, . As no living tumour cells have been preserved it is rather difficult to assess these findings with modern analytical tools . (C) Commercially probably the most interesting transmissible cancer was affecting bivalve molluscs was first identified in the 1970s and has caused a steep global decline in bivalves . The leukaemia-like disease has so far been identified in soft-shell clams, mussels, cockles and golden carpet shell clams at both sides of the Atlantic Ocean, as well as in the North Pacific Ocean , . Left to right: The common cockle (Cerastoderma edule), the soft-shell clam or sand gaper Mya arenaria, the pullet carpet shell (Venerupis corrugate). (D) The best-known transmissible tumour which also received extensive coverage in the popular press is doubtlessly the devil facial tumour disease (DFTD) in Tasmanian devils (Sarcophilus harrisii) -. First noticed in 1996, the disease had spread to more than half of the species' range by 2007 and by 2008 affected populations had been reduced by 89% .

Figure 3

Proposed workflow for the Animal Cancer Cloud (ACC), a potential project to harvest biomedical information from animal cancers. Proposed workflow of a project combining establishing a biobank of animal tumour samples, across a wide variety of species and tumour sites, including healthy controls and a data mining approach.

Figure 4

The potential future value of the Animal Cancer Cloud in the treatment of rare cancers. Rare human tumours which are too distinct in their (epi)genetic characteristics to allow the application of findings from common tumours might have analogues in animal cancers. Shown here as an example is a generic paediatric tumour compared to an adult disease, but this line of reasoning holds true for rare adult tumours, such as, for example, a Juxtaglomerular cell tumour, as well. Using the data accumulated in the Animal Cancer Cloud (ACC) an animal homologue with similar characteristics might be identified. If this is the case historical records might yield information beneficial for humans with regards to potential risk factors and treatment strategies. Information from the animal population might also be used in concert with human genetics to identify multifactorial genetic contributors to this cancer type, potentially leading to an early screening/prevention strategy in the at-risk human population. If the selected a) animal fulfils certain prerequisites, such as short life span and small body size and a large enough population exists or can be bred and b) the tumour is common enough or can be induced a clinical animal trial can be envisioned, where treatment options are evaluated in a genetically diverse population with the disease in its natural environment. It is expected that such trials would be superior to the traditional pre-clinical in vivo models and would allow a more efficient preselection for the clinical evaluation in humans. They would, of course, also create more data for the ACC. Finally, a population-based study would also produce additional information on associated risks for the animal tumour which could also contribute to our understanding of its human counterpart.

Figure 5

The immune system and infectious cancers. The role of the immune system has so far been studied in two of the four known forms of infectious cancer. Here, we have summarized the spares, partially contradictory information available.