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Regardless of the source of CTVT’s mutations, it has clearly accumulated a lot of them. Put it this way: Today’s tumors are about as genetically different from the founder dog as two distantly related dogs are to each other. “CTVT is like its own organism,” Murchison says. “It isn’t really a dog. Is it a cancer, still?”
There’s good reason to think that the answer is no. Sure, it’s a tumor, but one that behaves in very strange ways. For example, one of the hallmarks of cancer is genomic instability. That is, it is constantly mutating, duplicating or deleting genes, rearranging entire chromosomes. To look at a cancer genome is to stare at chaos. CTVT, by contrast, is a picture of stability. Yes, it has a lot of mutations, but that’s because it’s been around for thousands of years. If anything, it acquires new ones at a slower rate than you’d expect for a cancer.
Also, the majority of those mutations, including almost all of the recent ones, are neutral. They don’t seem to benefit the tumor in any way. Again, that’s very different from most cancers, which are constantly adapting to outfox their hosts’ immune systems, or to grow a little faster, or to spread to new areas. Not so with CTVT. “We think that the cancer is not adapting anymore,” says Adrian Baez-Ortega, who was one of the main researchers on the study. “Maybe it doesn’t really need to.”
Perhaps, early on in CTVT’s history, it found such thorough ways of escaping the immune system and jumping into new hosts that no further tweaks were necessary. Or perhaps it no longer imposes enough harm on its hosts to warrant a counterattack. It’s rarely fatal, after all, and if dogs are otherwise healthy, it doesn’t grow very fast. “The tumor and the dogs aren’t competing against each other anymore,” Baez-Ortega says. “They’re coexisting. The cells behave like cancer cells, but the ecology of the tumor is that of a parasite.” And a fairly benign one at that.
Doctors should take note. In lieu of aggressive chemotherapy, which drives the evolution of resistant and recurrent tumors, some researchers are looking at a strategy called adaptive therapy. Their plan is to treat cancers intermittently and gently, enough to control them, but not enough to trigger the rise of resistance. The goal is not to cure, but to tame—to turn a tumor into a long-term but manageable problem. And CTVT shows that “a tumor can be tamed by evolution,” Baez-Ortega says. It can evolve toward low-key survival instead of aggressive growth.
Its future is uncertain, though. While failing to acquire beneficial mutations, CTVT is also failing to weed out harmful ones. That’s understandable, because much of its DNA comprises genes for building a dog. It can afford to let those mutate into obsolescence. But over time, the genes that it still needs will also take hits. Slowly, the tumor will become weaker and less efficient.
Evolutionary biologists have long predicted that purely asexual organisms—those that reproduce by cloning themselves instead of having sex—are doomed to this fate, which is why they’re incredibly rare. CTVT seems to be proving them right. “Is it an evolutionary dead end?” wonders Hannah Siddle of the University of Southampton, who studies contagious cancers. “Is it gradually becoming more unstable under its increasing random mutational burden?” Baez-Ortega thinks so: “I don’t see this surviving for millions of years,” he says.
Humans have sped up the tumor’s demise by treating it with chemotherapy—a surprisingly easy feat because, unlike most cancers, it doesn’t seem to evolve resistance to drugs. Indeed, almost all the 546 dogs sampled in Murchison’s study were cured, even when their tumors had metastasized. “That’s astounding,” she says. “CTVT is probably one of the most curable cancers we know of.”
But I wonder, when we talk about cure, do we really mean extinction? CTVT is a unique biological entity—not quite a cancer, not quite a dog, and not quite like anything else. There’s a growing movement to protect unglamorous parasites alongside more charismatic fauna. Is CTVT, with genetic collapse on its horizon, a case for conservation instead of cure? Would anyone seriously propose saving a tumor?
“I think you could make that argument, but not at the expense of dogs’ welfare,” Murchison says. “They do recover, but chemotherapy is not nice. I wouldn’t personally be concerned if CTVT was eradicated from the dog population, but if it was kept in a museum, that would be ideal.
“It would be very sad if it disappeared from the planet,” she adds.