Elephants and cancer

Elephants

Image from flickr user pablo_marx under a Creative Commons CC BY-NC-ND 2.0 Licence 

This is something I wrote a couple of years ago, but never got around to publishing. Just been going through some old writing, so here it is.  

Cancer is a disease caused by genetic damage of cells causing runaway cell growth. These malfunctioned cells also have the capacity to invade other tissues (metastasis). For cancer to occur a couple of things need to go wrong in the cell –the cells divide when they shouldn’t and fail to carry out apoptosis (controlled cell death). Cancerous tumours also create signals to generate a bloody supply to maintain the tumour.

Cancer is the second biggest killer in the western world and plenty of time and effort has been invested in trying to prevent and treat it. We also know that almost all animals that we have looked in can get cancer. We have been aware for a long time that there’s an apparent paradox in the rates of Cancer across different species. Peto’s paradox states that if the chance of cells becoming cancerous was the same across different species, it would be expected that animals which are bigger and therefore have more cells would have more cancer, but repeated observations have shown that this isn’t the case. (Within species on the other hand, the trend does seem to be true – for instance there is a positive correlation between height and cancer rate in humans). For over 40 years we have been unsure why Peto’s paradox holds.

Clearly people haven’t looked in every species, but from the studies that have been carried out, we know that cancer risk is similar across most species. It is clear, however, that there are exceptions – for instance, studies of the extremely odd-looking naked mole rat have never conclusively identified a cancerous growth. Elephants have around 100 times as many cells as people do, which should increase the risk of them suffering the DNA damage that causes cancer. Elephants also have long lifespans – an average of around 60 years, which again, should stack the odds in favour of them getting cancer. But they rarely do – around 5% of elephants die of cancer compared to around 20% of humans (and that’s with all the advances we’ve made in treating cancer).

A recent study of the elephant genome has uncovered a possible explanation for the low risk of cancer in elephants. Asian elephants have 30-40 copies of a gene known as TP53 (short for Tumour Protein 53 – 53 is an estimate of its size, not indicative that there’s another 52 similar genes) compared to just 2 copies in the human genome. TP53 does several things to help protect against cancer – it can activate DNA repair mechanisms, it can arrest cell growth to give time to repair the DNA, and if that fails, it can initiate programmed cell death. So once the researchers found the extra copies of TP53, they wondered if all these extra copies allowed for super-efficient repair of DNA. It turned out that this isn’t the case – they found that DNA damage repair in elephant cells is no more effective than in human cells. On the other hand, the elephant cells with DNA damage were twice as likely to undergo controlled death, killing them off before they could potentially create a tumour. So it looks like the extra copies of TP53 allow elephant cells to be killed off if they get damaged.

So can we use this knowledge to help to treat cancer in people?  Well, we’ve known for a while that TP53 is an important anti-cancer gene, so efforts to target it with drugs are well underway. Given this latest research, efforts are now underway to see the effect of inserting extra copies of TP53 or whether compounds that replicate the effect of the extra copies can be identified. Furthermore, this study highlights that studies of cancer in other species, especially those species with exceptionally low cancer rates, can give us further leads to follow up on for potentially new cancer prevention and treatment.

See the paper here: JAMA. Published online October 08, 2015. doi:10.1001/jama.2015.13134

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