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Cover-photo credit: Josh Mazza, 2015

 

I recently came across an interesting article. The title boldly stated that “elephants don’t get cancer,” which at first caught my eye, admittedly because I figured it was a click-bait and I am a bit of a skeptic when it comes to these sorts of articles. But then, after reading it and doing a bit of my own research, it made me feel warm and fuzzy, and I’ll tell you why. Not only are they my favourite animals, but also because I’m looking forward to the new research in the field that will ultimately lead to promising cancer treatments and discoveries.
So, let’s get to it – what’s the deal with that bold statement?

According to an article published in JAMA in 2015, researchers examined 36 mammalian species, which included animals in varying sizes – from mice to elephants and a few in between (1). The study looked at whether the risk for cancer increased with increased body size, and in particular, why elephants don’t develop cancer at the same rate as humans (1). The idea that as cell count increases, as does the incidence for mutation and risk for developing cancer may sometimes be assumed if one were to follow the idea that all mammalian cells have equal susceptibility to mutation. However, the study did not confirm this idea (1). The lack of correlation between the two variables is known as  “Peto’s Paradox” (2). In fact, according the Elephant Encyclopedia Database and as stated in the study, it was found that when examining deaths of documented elephants (n=644), the cancer incidence during the lifetime of the elephants was less than 5% (1). What makes this so astonishing is that, despite having a significantly larger body mass and therefore, more cells prone to mutation, this value is drastically lower than what we find in human subjects.

 

So what’s the deal – what’s the secret of this nearly cancer-free species?

The secret, researchers believe, may lie in the TP53 gene. The role of this gene is to suppress tumours, and the gene present in humans – though we only have two, whereas elephants have many (1). In humans, when cancer cells are detected by the body, the TP53 gene intervenes, and begins to first repair, then slow or stop proliferation, and if unrepairable, induces cell-death, or apoptosis  (1). In elephants, however, the gene is amplified, in a sense – the signalling pathway is almost hyperactive, and reacts quickly to mutations by simply killing off the cell when it appears to have damage (3). Besides the many TP53 genes present in elephants, the process in the elephant, when compared to the human, seems almost more efficient: the elephant’s TP53 gene activity reduce the risk of the body ineffectively “treating” and “fixing” the cells, which could later turn into cancer (3). Elimination, in this case, may be the best bet.

What does this mean for us, and why should you care?

If scientists are able to create a drug that mimics the effects of the TP53 gene of the elephant and administer it to human subjects that are particularly prone to developing cancer, such as those with Li-Fraumeni disease, then patients have a better chance at winning their battle. Though the results from the study are still preliminary and more research needs to be conducted, it’s an exciting step on the road to ending cancer. Three cheers for science!

 



 

References:

(1) Abegglen, L. M., Caulin, A. F., Chan, A., Lee, K., Robinson, R., Campbell, M. S., … & Jensen, S. T. (2015). Potential mechanisms for cancer resistance in elephants and comparative cellular response to DNA damage in humans.JAMA, 314(17), 1850-1860.

(2) Caulin, A. F., & Maley, C. C. (2011). Peto’s Paradox: evolution’s prescription for cancer prevention. Trends in ecology & evolution, 26(4), 175-182.

(3) Sulak, M., Fong, L., Mika, K., Chigurupati, S., Yon, L., Mongan, N. P., … & Lynch, V. J. (2015).  TP53 copy number expansion correlates with the evolution of increased body size and an enhanced DNA damage response in elephants. bioRxiv, 028522.

 

 

 

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