The animals that live beside us have secrets to tell about the causes and cures for cancer.
Joshua Schiffman, a pediatric oncologist at Primary Children's Medical Center and Huntsman Cancer Institute in Salt Lake City, had never given a second thought to animal medicine, until his dog Rhody was diagnosed with histiocytic sarcoma three years ago. The cancerous tumor spread quickly, and the big, lovable, Bernese Mountain Dog died just 4 months later. Soon after, Schiffman stumbled across a study identifying the genes that cause nearly one quarter of the dog breed to develop this cancer.
“Everything snapped into place,” says Schiffman. “I thought to myself, these dogs are just like the patients I’m taking care of and studying everyday.” He treats patients with hereditary cancer, including those with sarcomas similar to Rhody’s. The disease is devastating to both dogs and people, attacking the skin, bones, lungs and other organs.
The emotional journey launched Schiffman headlong into a growing movement. Scientists are turning to wild and domestic animals in search of new insights into the causes and cures for human cancer and other diseases. Now, alongside human patients, Schiffman researches cancer in dogs, sea lions, and elephants.
Learning Tricks From Dogs
“I like to say it is the patients that guide your career,” remarks Schiffman. “In my case, that patient was also my dog.” His experience motivated him to learn how dog genetics could help people with hereditary cancers, some of whom have an 80-90% risk of developing the disease, many during childhood.
He contacted an author of the Bernese Mountain Dog study, Matthew Breen, a professor of genomics at North Carolina State University, and was surprised to learn they had been living “parallel lives.” In search of new inroads to treating cancer, both investigate how tumors change genetically over time. Only Breen does so in dogs, and Schiffman in people.
As tumor cells divide uncontrollably, they accumulate numerous genetic changes. While some are harmless, others give cells the power to survive, grow faster, and spread. The trick is to distinguish the so-called “drivers” of disease progression because they are ideal candidate targets for new cancer therapies and treatments.
The veterinarian and doctor are now combining resources to fight histiocytic cancers. Unlike in Bernese Mountain Dogs, the disease is rare in humans, occurring at a rate of about 1 in 200,000. And that is precisely why the study is so valuable. It would be difficult to gather enough data from human patients to hone in on meaningful targets for therapy.
“Samples from human cancer patients are helping us to refine the data that we’ve got in the dogs,” explains Breen. “They will help identify the subset of genes that clearly have an impact in both species.”
The comparisons won’t stop with histiocytic cancers. Boxers are at high risk for brain cancer, rottweilers for bone cancer, and Scottish terriers for bladder cancer. The researchers will be working together to mine the genomes of each breed for pathologically relevant genes in humans.
Into The Wild
Each species can tell us something different about cancer. Because domestic and wild animals breathe our air and live in our waters, they share the same environmental risk factors for the disease. When any of these animals have high rates of cancer, it could be cause for worry.
Each year, hundreds of sickened California sea lions wash up onto the western U.S. coastline. Nearly 20% of those that die in animal hospitals have an aggressive cancer of the reproductive and urinary tracts. “It looks like the whole abdominal cavity has been packed full of cauliflower,” says Breen, a member of the Sea Lion Cancer Consortium. “It’s just completely riddled with horrible looking cancerous tissue.”
Breen has determined that the sea lion cancer shares genetic mutations with bladder and kidney cancers in humans and dogs. Others have found that the sea lions have high concentrations of organic pollutants in their blubber. “It will be interesting to assess if people exposed to high levels of organic pollutants similarly start to develop more bladder cancers," says Breen.
Schiffman and Breen are now testing whether aberrant genes shared among the three species' comparable cancers actually play an active part in human cancer progression. Any new therapies could be tested in dogs first and brought to humans if those trials are successful.
Breen remarks, "We really need to pay closer attention to the health of the animals who share our environment as we can learn a great deal about possible environmental impacts to our own health."
While sea lions are revealing how cancer arises, elephants may hold insights into cancer prevention. According to evolutionary theorists, large-bodied, long-lived animals are a living conundrum. Elephants have roughly 100 times more cells than humans, and so would be expected to get cancer 100 times more frequently. In fact, by some estimates 13% of people worldwide die of cancer, and only 4% of elephants do.
Schiffman is collaborating with the Hogle Zoo in Salt Lake City to discover how elephants beat the odds. “Elephants had millions of years of evolution to learn how to avoid cancer, and now we're studying their secrets in the laboratory to apply it to our human patients," he says.
Every species has a cancer story to tell, comparative medicine gives them a voice.
Rhody with Schiffman's children (photo credit: Joshua Schiffman)