Devil Facial Tumor Disease Turns Endemic

Researchers at Washington State University in Pullman have reported that Tasmanian devils may no longer face extinction from devil facial tumor disease (DFTD), a transmissible cancer. Rather, this disease seems to be settling into an endemic phase. Studying DFTD could prove informative for human tumor biology and therapeutics, even if cancer transmission among humans is rare.

First identified in 1996, DFTD is “spread via an allograft when devils bite each other during social interactions,” explains senior author Andrew Storfer, PhD. It occurs throughout the island of Tasmania and is “almost invariably lethal” to these stocky marsupials. Contagious cancers are nonetheless rare in the animal kingdom; the only other known types are canine transmissible venereal tumors (CTVT) in dogs and bivalve neoplasias in clams, cockles, and mussels.

In this study, Storfer says, “we adapted phylodynamic analysis, typically deployed to track the spread of viruses, to a much larger genome [DFTD].” The researchers screened 11,359 genes, pinpointed 28 that had “evolved in an appropriate clocklike manner,” then used the selected genes to estimate DFTD's R_E, or effective transmission rate. They found that R_E was initially as high as 3.5—“consistent with when the disease was discovered,” Storfer observes—then declined sharply to about 1 at present, “suggesting that DFTD is transitioning from an epidemic, outbreak-type phase” to endemism.

This shift could be a consequence of population decline, with fewer devils to spread the disease. Alternatively, David Hockenbery, MD, of Fred Hutchinson Cancer Research Center in Seattle, WA, points out that CTVT, “which has been around for thousands of years, is thought to have evolved to this quasi-balance between not killing dogs and remaining transmissible. Could devils be reaching a similar coexistence with DFTD?” If so, uncovering how and why might illuminate “ways to treat human cancer as a chronic disease—not always getting rid of the last tumor cell, but achieving this equilibrium where our host defenses can keep things in check.”

Michael Metzger, PhD, of Pacific Northwest Research Institute in Seattle, offers this hypothesis: “Devils could be becoming resistant to an otherwise fatal disease; perhaps those with protective polymorphisms are favored in natural selection.” His group has observed that whereas a bivalve transmissible neoplasia led to high mortality rates over a short time in soft-shell clams across New England and Prince Edward Island, Canada, the prevalence is now much lower. “We're trying to figure out why.”

For Metzger, Storfer's study is exciting. “Any species that can evolve to resist cancer is one I'd want to know about. It will likely inform therapeutics in some way—whether it's human orthologs of the genes that are involved, or other insights we wouldn't gain using current models.”

Hockenbery agrees. In an earlier collaboration, he and Storfer linked expression of RASL11A, a RAS family tumor suppressor gene, with DFTD's rare spontaneous regression. RASL11A is downregulated or silenced in human prostate and colon cancers, they note. The current study has yielded “new candidates for downstream validation”—for instance, NAALADL2, which may influence oncogenicity in devils and humans.

As well, “it's become apparent that MHC class I/II is downregulated in devil tumors, something also seen in humans,” Hockenbery says. He and Storfer have established a devil genome-wide CRISPR library to hunt for genes that, “when deleted, would allow MHC reexpression. It would be interesting to compare these genes, if found, with the human situation.”

In general, “DFTD behaves similarly to human cancers,” Storfer remarks, “so whatever we learn could have applicability down the road, albeit with many [lab research] steps in between.” –Alissa Poh

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