There's an absolutely amazing essay by Carl Zimmer that just went up on his Discover blog The Loom, about how blue whales are a seemingly impossible creature. Though they are tremendously huge and can live to be over 200 years old, they rarely develop cancer. Zimmer writes:
Blue whales can weigh over a thousand times more than a human being. That's a lot of extra cells, and as those cells grow and divide, there's a small chance that each one will mutate. A mutation can be harmless, or it can be the first step towards cancer. As the descendants of a precancerous cell continue to divide, they run a risk of taking a further step towards a full-blown tumor. To some extent, cancer is a lottery, and a 100-foot blue whale has a lot more tickets than we do . . .
Caulin and Maley argue that when animals evolve to larger sizes, they must evolve a better way to fight against cancer. It's possible that a blue whale simply has a souped-up version of our own defenses. We have proteins that monitor our cells for over-eager growth, for example; they can kill or zombify cells that on the road to cancer. When the genes for these gatekeeper proteins mutate, a cell becomes more likely to become cancerous. The opposite also seems to be true: Scientists have engineered mice to have extra copies of these gatekeeper genes, and they've found that the animals become more resistant to tumors.
Caulin and Maley suggest that nature has carried out this experiment as well. We have one copy of a gatekeeper gene called TP53, for example. Elephants–which are at a greater risk for cancer–have a dozen copies of the same gene.
Other defenses might include a more powerful immune system that can destroy new tumors. Big animals may have also lost some genes that make them particularly prone to developing cancer. And anatomy itself can offer a defense, Caulin and Maley point out. As the cells in each colon crypt divide, for example, the older ones get pushed up to the top and get sloughed off. As a result, there are few steps from stem cell to the final cell in a lineage. With fewer steps, we run a lower risk of developing cancer. Bigger animals may have evolved even more effective architectures.
It's also conceivable that big animals enjoy defenses to cancer merely by being big. Big animals have a lower metabolic rate for their weight than smaller animals. With a lower metabolic rate, big animals produce fewer harmful byproducts that can cause mutations. One pretty wild benefit of being big has been proposed by John Nagy and his colleagues: big animals can kill cancer with cancer. Nagy's idea is that tumors can develop "hypertumors"–cancer cells that parasitize their fellow cancer cells.
Find out more by reading Zimmer's post on his blog The Loom.