|Courtesy of Matt Biddulph CC BY-SA 2.0|
Joshua Schiffman, a pediatric oncologist at the University of Utah's Huntsman Cancer Institute, was always puzzled by the fact that elephants rarely develop cancer. The disease, after all, is triggered by abnormal cell growth, therefore the more cells an animal has, the more susceptible it should be to the disease, he thought. Now Schiffman may have an explanation for elephants' incredible resistance to cancer.
In a study published in the Journal of the American Medical Association, Schiffman and his co-authors determined that elephants have 38 extra copies of a gene that encodes p53, a well-known tumor suppressor. Humans have only two copies of that gene. That could explain why elephants have an estimated cancer mortality rate of 4.8%. In people, the cancer mortality rate is as high as 25%, according to the study.
"Nature has already figured out how to prevent cancer. It's up to us to learn how different animals tackle the problem so we can adapt those strategies to prevent cancer in people," Schiffman says in a press release from the University of Utah.
To complete the research, the authors coordinated with Utah's Hogle Zoo and Ringling Bros. Center for Elephant Conservation, using blood samples collected from the elephants during routine checkups. They took white blood cells from the samples and subjected them to DNA damage, which typically would trigger a cancerous response. Instead, the cells committed suicide--a response that was likely mediated by p53, the authors say.
Scientists have long been aware of p53's tumor-suppressing powers. In fact, several biotech companies have devised ways to reactivate p53, but their efforts to turn those innovations into usable therapies have been plagued by challenges.
One company that has attracted support for its p53 strategy is Aileron Therapeutics of Cambridge, MA. The company recently raised $48 million in a Series E funding round to advance its drug candidate, which aims to reactivate p53 by targeting two so-called suppressor proteins. The company has shown in preclinical studies that its drug works in tumors that overexpress those proteins. Human trials started last year.
Whether gaining a better understanding of how elephants resist cancer will help improve the success rate of p53 research remains to be seen. But there's little doubt that studying diseases that are common among people and animals can stimulate scientific progress. Schiffman is a supporter of comparative oncology, a field of research that promotes collaborative research between veterinarians and scientists who study human cancers.
There have been a number of developments in comparative oncology of late, including a recent study led by the Broad Institute of MIT and Harvard, which identified several genes among both dogs and people who suffer from lymphoma and leukemia. The researchers also discovered novel genes that could lead to new treatment strategies for those cancers.