The Common Cure

Cats and dogs get many of the same cancers we do. Could they be the key to unlocking new treatments that help us — and our pets — beat the disease?

With dogs and cats, cancer therapies are usually more palliative than curative. For Foxxy the toy poodle, surviving a year past her diagnosis means she’s beat the average for dogs with lymphoma.

Foxxy, the caramel-colored, seven-pound toy poodle spent her first four years as a care-free lapdog at the center of a retired couple’s life. Year five, however, was earned.

The four-page handwritten log of chemotherapy is proof: 34 treatments, which Eric Woodward, Foxxy’s owner, can nearly recite from memory, fill the narrow ledger lines.

He easily weaves the hard-to-pronounce names of half a dozen drugs into an informal oral patient history, which as of yet, has no definitive conclusion — other than that Foxxy is still here with enough pep to beg for doggy treats. Woodward thinks that alone is worth celebrating.

To mark her sixth birthday, roughly the one-year anniversary of her first chemo treatment for lymphoma, he delivered five-and-a-half dozen cupcakes to Foxxy’s “fan club” at the Bloomfield Hills clinic where she’s been receiving treatment.

“We’ve now made the average,” Woodward says a little cautiously of Foxxy’s life expectancy milestone. “A year from now, if we can keep her going, we’ll do cupcakes again.”

Woodward remains relatively upbeat about Foxxy’s diagnosis — proudly explaining how few side effects she’s had from all the medications; and how he had a blend of Chinese herbs turned into pills at a local compounding pharmacy when they proved too bitter to hide in peanut butter. He also, in the course of a half-hour discussion, makes multiple references to an experimental new treatment that could soon be available if the USDA greenlights it. But the reality is Foxxy is running out of options.

“This dog has had a lot of chemo and failed a lot of chemo,” oncology tech Jessica Billington says today, administering Foxxy mitoxantrone, one of the only drugs they haven’t tried. Her lymphoma has been resistant to nearly everything else, and the dog’s lymph nodes have started to get bigger again, a sign that the cancer could be getting the upper hand. If the drug works, Foxxy could earn some more time, but for dogs that have already relapsed, Billington says the chances aren’t great. At any time, the oncology team could be left looking for a segue into a discussion about end-of-life.

It’s a routine turn of events for pets with cancer, although Foxxy’s oncologist, Michele Sauerbrey, says it often catches owners by surprise. “The ultimate goal for cancer treatment with people is curative,” she says. “But with our pets, the care is usually more palliative — meaning we’re trying for minimal side effects from treatment and to maintain quality of life.” For lymphoma patients in particular, life expectancies post-diagnosis are usually measured in months, occasionally in years, and more rarely, with indefinite periods of remission.

There are many reasons: Cancer in cats and dogs tends to develop more rapidly than in humans, and often isn’t detected until its final stages. And more advanced treatments for animal cancers, like chemotherapy, are mostly derived from human medications, often older ones, which are themselves imperfect instruments.

But some researchers think the reason human treatments work at all for cats and dogs — the fact that we get many of the same cancers, and more fundamentally, that we are genetically similar creatures — could be the key to unlocking a paradigm shift in how we fight cancer.

Humans get many of the same diseases as our companion animals, but research partnerships between vets and medical researchers have been relatively few. Veterinary oncologist Michele Sauerbrey (above, center) and researchers Wei-Zen Wei and Heather Gibson (below right) say more collaboration could lead to better therapies for certain kinds of cancer.

Common Bonds

Currently, the relationship between humans and pets is a one-way street: Cats and dogs are merely the recipients of human cancer drugs, administered in lower doses. But our companion animals generally don’t factor in during the development of those medications. That role, of course, has fallen mainly to mice, which have played guinea pig in cancer labs for more than half a century.

Despite their dominance, mice can be blunt tools for modeling certain kinds of human cancers, according to Heather Gibson, a research scientist in Dr. Wei-Zen Wei’s lab at the Karmanos Cancer Institute and Wayne State University. The Wei lab experienced this firsthand when they were developing an immunotherapy vaccine, which works by coaxing the immune system to recognize and destroy cancers linked to a protein-coding gene called HER2.

“When you get a vaccination against a virus, your immune system will respond robustly and kill it with no problem,” Gibson says. “But for cancer, it all originates from your own cells. And in the case of HER2, the protein itself is not mutated — it’s just expressed in abundance — so it looks normal. As a result, you have to coerce the immune system to break one of the cardinal rules and attack the body’s own tissue.”

That alone is a huge challenge. But when the team moved forward with testing their vaccine in mice — an important step in any research trial — they had to confront another big obstacle.

In humans, HER2 functions as an “oncogene,” meaning it naturally causes a variety of cancers, including about 30 percent of breast cancer, ovarian cancer and certain forms of stomach, head and neck cancers. However, in mice, HER2 isn’t a natural cancer trigger. So to even test their vaccine, the team would first have to figure out a way to make mice get HER2-based cancers.

Ultimately, it involved some weird — and expensive — science: First they engineered special mice with the human HER2 gene, and then implanted their test subjects with lab-grown tumors modified to express human HER2.

At that point, the team introduced its vaccine to see if it could coax the mice into having the desired immune response. When the early rodent trials looked promising, they moved the vaccine to a human clinical trial. But that’s where they ran into a common speed bump — one that happens all the time in cancer research, where only about 10 percent of clinical trials result in new therapies. The immune response in human patients wasn’t nearly as strong as it was in mice, indicating that whatever was happening in the rodents, wasn’t happening in humans.

For the team, it meant potentially having to circle all the way back: Tweaking the vaccine in the lab, then moving it to another rodent trial, then back to human clinical trials and hoping they wouldn’t strike out again. Of course, doing all of this could take years and hundreds of thousands of dollars.

“So Dr. Wei said to the team, ‘OK, maybe we need to find a better model where we can actually test these vaccines in some other real-life disease system,’” Gibson says. They came across feline mammary carcinoma. Under a microscope, the tumors look very similar to human breast cancer.

An Unlikely Match

Cats, it turns out, get breast cancer too. They also — unlike mice, and like humans — develop HER2-linked breast cancers naturally. This meant the research team could potentially skip the complicated and expensive process of genetically engineering mice and growing tumors, and instead study their vaccine more directly in cats.

In fact, cats have several advantages over mice. First, cats with mammary cancers usually relapse within six months to a year after they’re treated, meaning the team wouldn’t have to wait long to see if their vaccines could prevent a rebound of the cancer.

Cats and humans also have another key thing in common: We’re both “outbred” animals, meaning our larger populations contain a lot of genetic diversity. With strains of lab mice, all the individuals are bred to be genetically identical. This helps researchers control for other genetic variables in early research, but a possible side effect is positive initial tests that don’t extrapolate.

“When you’re working with one specific strain of mice, and they’re genetically identical, that represents one human being in my opinion,” Gibson says. “We realized that if you have two different strains of mice, one of them can respond really well, and the other one barely responds at all. The only difference is their genetic background. That was our first hint that we should try working with an outbred population.”

In short, because cats are much more like humans than mice are, Gibson says they could be better subjects for modeling certain cancer treatments. But how that would actually happen in labs would follow a much different paradigm. Instead of breeding animals in-house and artificially introducing tumors, cancer researchers like Wei and Gibson would work alongside veterinary oncologists, who have pet patients with naturally occurring, terminal diseases that parallel human cancers. With pet owners’ consent, animals would then receive a new experimental therapy as part of a research trial.

A New Paradigm

It’s an emerging model of vet-doctor collaboration known as comparative oncology. And in this case, the research team reached out to Sauerbrey, Foxxy the poodle’s oncologist, who helped recruit owners of several cat patients with naturally occurring HER2-linked mammary cancers.

The research lab covered costs for mastectomies for the cat patients, a first-line surgery that’s routine in cat breast cancer treatment (but one which many owners skip because of the high cost). In return, the team examined the tumor samples to determine if any of them might be good candidates for their vaccine.

Early experiments with the tissues proved promising — so much so that Wei, Gibson, and Sauerbrey would now like to move forward with a veterinary trial that tests the vaccine directly in cat patients. But they’ve since run into another common road block in cancer research: funding.

“Up until recently, funding for comparative oncology studies has been scarce,” Gibson says. “But it’s getting better. Now, cancer research funding agencies are actually looking for people who are doing these kinds of studies. Europe’s actually been doing these kinds of studies for a few decades. So slowly, I think we’re starting to pick up on the fact that there might be something to this.”

The Way of the Future

Though mice will continue to play a key role in research, Gibson has a hard time believing that, in time, comparative oncology won’t become a common tool in cancer labs.

For one, it could shave years off the process of getting treatments to human patients. Currently, when researchers file the paperwork for a human clinical trial, it can take years for the FDA to give them the go ahead. And while they’re waiting, a lab could make dozens of discoveries that improve a treatment.

“But at that point, you’ve already started the trial with the original form of the drug, and you’d have to begin the whole [FDA application] process over again,” she says. “We’ve learned quite a bit since our vaccine originally went to clinical trials in humans. There are at least six things I can quickly think of that, had we known and implemented, [the vaccine] may have worked better.”

With veterinary trials — which are overseen by the USDA, not the FDA — there isn’t as much red tape. Because of this, Gibson says a lab could actually introduce modifications to treatments during a clinical trial.

One model for a comparative oncology-based system would be to insert the pet trials in between rodent and human clinical trials. [The latter would still need FDA approval.] This way, vaccines or drugs could be developed with rodents, then fine-tuned in cats and dogs. Dead-end treatments would get weeded out with a less expensive veterinary study rather than a human trial.

And because cats and dogs are often better models for humans anyway, the treatments worth moving to a human trial would likely be more effective to begin with.

Another strength of this approach is that our cats and dogs would be among the main beneficiaries of the science. Because nearly all cat and dog cancer treatments are derived from human ones, our companion animals could expect new, better treatments for their own cancers. In fact, they would likely have access to experimental treatments before humans would.

“I don’t actually look at it like our pets are guinea pigs,” says oncologist Michele Sauerbrey. “I think it’s a real opportunity for us to collaborate a lot more. And not only with cancer. Diabetes and a slew of other diseases are actually very similar in humans and our pets. I think it’s a lot of wasted effort that there hasn’t been more collaboration earlier.”

In fact, Sauerbrey is already seeing the results of a handful of comparative oncology projects filter into her clinic. In one case, veterinary and human oncologists teamed up to produce a medication that’s an effective therapy for dogs with certain kinds of mass-cell tumors. And for dog patients with some melanoma, there’s now the option of a DNA vaccine that has greatly increased the survival time for some patients. That treatment was a result of a collaboration between a veterinary scientist and cancer researchers at Memorial Sloan Kettering University in New York City.

The breakthroughs are still relatively few, and until more arrive, many animals Sauerbrey treats will end up with their pictures on the bulletin board in Exam Room 1.

Here, dozens of photos hang alongside appreciative messages that all seem to echo each other. On first glance, it’s uplifting to see the love people have for their pets, and their gratitude for the care they got during a difficult time. Then it hits you.

“All the photos are of dead patients,” says oncology tech Jessica Billington as she finishes up Foxxy the poodle’s latest round of chemo. “But it’s not sad to us. We form relationships with these people, and I think they just want to make sure we have the memory forever.”

Billington then offers Foxxy a reward for completing treatment No. 35 — a chicken doggie treat, her favorite — then lightens the mood. She points to the other infamous wall of photos in the office, the one in the chemo treatment room full of awkward pictures of the staff (including Michele Sauerbrey’s senior portrait, the doctor stretched out over the hood of a white Corvette, sporting some serious ’80s big hair).

It’s a shrine of levity to rally around while they wait and hope for another little dog to defy the odds — and a future where humans and our animals help each other beat cancer.