New ways to fight cancer.
Rats, bats, elephants, whales may help explain human risk
FRIDAY JULY 27 2018
ELEPHANTS have 100 times as many cells as humans. But they seldom get cancer. This is surprising, because cancer is a result of cell division gone wrong, and the more cells an organism has, the higher the chances that some will mutate into tumours. Also, because elephants live so long – between 60 and 70 years – their cells have more opportunities to mutate.
The counter-intuitive observation that cancer risk does not always correlate with a species’ size or longevity is known as Peto’s Paradox, named after British epidemiologist Richard Peto.
It turns out that cancer does not strike all species equally: some animals have evolved powerful strategies to keep the disease at bay, while others are particularly vulnerable.
Scientists are increasingly exploring this interspecies variation in cancer rates, hoping to learn more about how cancer works in humans and to identify better ways of treating or preventing it.
“Elephants should be getting cancer all the time,” said University of Utah cancer researcher Joshua Schiffman. “But they don’t. They’ve evolved some really effective anti-cancer strategies.”
Schiffman and colleagues have found that elephants have 40 copies of the TP53 gene, which suppresses tumour cells before they can grow and spread. By comparison, humans and most other animals have only two copies.
Scientists have long known that TP53 helps the body kill rogue cells before they can transform into tumours. The elephants’ approach appears to be a unique evolutionary strategy for fighting cancer.
Schiffman and colleagues found that elephants also have other anti-cancer mechanisms. Elephant cells respond differently when exposed to substances that damage DNA. Instead of trying to repair the damage, they tend to simply die.
With cancer, this is a much safer approach: cells that try to heal themselves are more likely to mutate and then transform into cancer cells.
Elephants are not the only animals with unusually low rates of cancer. Using data from zoos and veterinarians as well as anecdotal reports from the wild and lab research, scientists know or suspect that other creatures, including mole rats, grey squirrels, horses, whales and bats, rarely get cancer.
It is not entirely clear where humans fall on the spectrum of risk. For humans, the lifetime probability of having cancer is about 50%. While we do have some cancer-suppressing genes, we also tend to live for a relatively long time. For most animals, the lifetime cancer risk is probably between 20%-40%, with outliers on each end – elephants on one side and dogs, mice and cheetahs on the other.
Of course, cancer is tracked much more systematically in humans than in other species. “We just don’t have that much data from nature,” said University of California at Riverside biologist Leonard Nunney, who studies evolution, animals and cancer and coined the term “Peto’s Paradox”. “So it’s very hard to compare.” Perhaps the strangest animal being studied for its cancer-fighting abilities is the naked mole rat, a 13cm-long, hairless, pinkish rodent that lives in burrows in East Africa. These creatures survive far longer than most rodents – up to 32 years – and seldom get tumours.
Over decades, scientists have studied thousands of naked mole rats in labs and zoos around the world; in that time, they have documented only six cases of cancer.
Naked mole rats also have an unusually powerful version of a gene called p16, which prevents runaway growth of tumour cells, and have also evolved a further strategy: if cancerous cells somehow get past hyaluronic acid and p16, mole rat cells have a fail-safe switch that causes tumours to essentially deactivate themselves, a state known as senescence.
Other researchers examining certain bat species have located several tumour-suppressing genes. A recent study of the bowhead whale, which weighs up to 100 tons and can live for more than 200 years, identified several genes that probably improve the creature’s ability to repair DNA mutations.
The slower metabolism of large animals such as elephants and whales may also play a role in their lower cancer rates: more intense energy production leads to more cell division, and thus a higher risk of mutations. Just as some creatures are more adept at fending off tumours, others are particularly vulnerable: more than half of all golden retrievers die of cancer, Scottish terriers are 18 times as likely as the average dog to get bladder cancer, and Irish wolfhounds are 100 times as likely to get bone cancer.
One of these mutations, which plays a role in 85% of canine bladder cancers, also exists in humans. The ultimate goal is to develop new ways to fight human cancer. – Washington Post