Cancers that can jump from one animal to another of the same species are rare, but the endangered Tasmanian devil is doubly unlucky: in the last few decades, two transmissible cancers affecting them have been identified. A comparison of these two cancers, published April 9 in the journal Cancer Cell, suggests that they are similar in origin, leading researchers at the University of Cambridge to believe that devils simply may be at greater risk for these kinds of diseases. The researchers also identified drugs that are effective against the cancers and could potentially be used in the fight to save the devils from extinction.
Tasmanian devils, while relatively docile with humans, are known for biting each other on the face as they fight over mates and food. This is the route by which both cancers, which cause similar facial tumors before metastasizing, spread from devil to devil. But even though the cancers manifest similarly, they originated in two different individuals, probably years apart.
There are only eight known naturally occurring transmissible cancers: one in dogs, two in Tasmanian devils, and five in various species of marine bivalves, so to see two such cancers appear in such a short time in a single species was quite surprising. "When the first one was discovered, we thought that transmissible cancers were extremely rare and that Tasmanian devils were just really unlucky to get this cancer," says senior researcher Elizabeth Murchison, a geneticist at the University of Cambridge who grew up in Tasmania. "But the emergence of the second one made us wonder whether Tasmanian devils might be particularly at risk for developing this kind of disease."
It was also possible some sort of environmental or anthropogenic change affecting the devils might have made the emergence of these cancers more likely. To evaluate these hypotheses, the researchers conducted genetic and functional comparisons of the two devil cancers.
They were unable to identify genomic markers of any viruses or external carcinogens, like UV light, that might have caused the cancers, although the researchers readily point out that there could be something they didn't test for or look for that does play a role. What they did find, however, was that the two cancers, despite originating in different individuals, had similar mutational processes and similar tissues of origin, and responded to similar drugs. "It really pointed to some kind of problem that the devils have with this kind of cell's regulation, which probably gives them a greater risk of developing this type of disease," Murchison says.
And it might all come back to that biting behavior. The effective drugs that the researchers identified when they compared the cancers inhibit pathways normally involved in healing, suggesting that wound repair pathways might somehow be involved in the origin of the cancers. So the devils' frequent facial injuries could actually play a role in causing the cancer to arise, as well as providing a route by which the diseases can jump from host to host.
Humans may have played a role, too. "When white people first settled in Tasmania, they'd hear these screams at night. And they thought there must be a devilish creature out there," says first author Maximilian Stammnitz (@DevilsAdvoMax). The settlers persecuted the devils, and the subsequent decline in their population probably further decreased the already low genetic diversity of the species. This is important, he says, because transmissible cancers need to escape the new host's immune system, just as any other foreign tissue transplant would in order to take hold. "Their immune systems may be less poised to detect foreign tumor cell grafts, compared to other species that have more genetic diversity." Furthermore, the changes to the landscape that have resulted from European settlement in Tasmania may have indirectly altered devil population dynamics and migration patterns, possibly creating conditions conducive for transmissible cancer emergence and spread.
The effects of these cancers have been devastating, wiping out 90% of the devils in some parts of Tasmania and threatening the survival of the species. "As scavengers, they're an important placeholder in the ecosystem of the island. They're sort of the ecological clean-up service, so their absence is visible in the landscape," Stammnitz says. While conservation efforts are already underway, the researchers are optimistic that, with further research and testing, the drugs their comparison has identified--which are currently used for precision cancer therapy in humans--could provide another option for helping the devils.
This research also has broader implications for our understanding of transmissible cancers. "Just in the last couple of years, we've gone from knowing of two transmissible cancers--the dogs and the devils--to eight. It's hinting at the possibility that perhaps transmissible cancers were not so well recognized before, and maybe they're more common than we previously thought," says Murchison.
This work was supported by grants from Wellcome, the National Science Foundation, Eric Guiler Tasmanian Devil Research Grants, a Philip Leverhulme Prize awarded by the Leverhulme Trust, the Gates Cambridge Trust, CRUK, and SU2C.
Cancer Cell, Stammnitz et al: "The origins and vulnerabilities of two transmissible cancers in Tasmanian devils" http://www.cell.com/cancer-cell/fulltext/S1535-6108(18)30117-X
Cancer Cell (@Cancer_Cell), published by Cell Press, is a monthly journal that provides a high-profile forum to promote major advances in cancer research and oncology. The journal covers topics related to molecular and cellular mechanisms of cancer, mechanisms for the sensitivity and the resistance to cancer therapies, development of better cancer therapies, and clinical investigations. Visit: http://www.