How beagles and goldens could help researchers find the next cancer therapy for humans

DAVIS, Calif. — Radiation oncologist Dr. Michael Kent desperately wants to beat cancer. He’s testing the latest high-tech treatments in clinical trials and using a multimillion-dollar linear accelerator so he can offer the best care to patients — whether they’re beagles, golden retrievers, or the black and white terrier mix named Moo he’s now treating for a recurrent tumor in her paw.

Kent is a veterinarian. Frustrated by the lack of treatment options for dogs with certain tumors and cancers that have metastasized, he’s searching hard for new treatments to extend the lives of his patients. But because the biology of dogs and humans is so similar, what he finds here at the UC Davis School of Veterinary Medicine could well help treat human cancers as well.

“For a long time, we’ve looked at humans to see how to treat dogs,” Kent said. “We’re starting to do a little bit of the reverse now.”

This field of comparative medicine — using animals to better understand and treat human disease — is not new; creatures such as mice, rats, and actual guinea pigs have long been the mainstay of medical research and studies of experimental drugs. What’s different is that veterinarians are now conducting rigorous clinical trials of new treatments with the hope they might eventually benefit humans as well as the family pet. Increasingly, they’re using dogs and cats and other companion animals in these experiments, as medical researchers recognize the limitations of traditional lab animals.

This work comes at a critical time, those in the field say, because so few oncology drugs — or drugs for many diseases for that matter — end up getting approved for use in humans after showing early promise in lab studies.

“There’s things we find in the lab that we think might be helpful, then we get to the clinic and they either don’t work or are toxic,” said Dr. Arta Monjazeb, a radiation oncologist at UC Davis Comprehensive Cancer Center who’s partnered with Kent to test new treatments in dogs. One immune therapy that the two recently tested to shrink metastatic lung cancer in his dog patients will soon enter clinical trials in humans at Davis.

While Monjazeb never expected to be working alongside veterinarians when he entered medicine two decades ago, he said he’s embraced work with pets in hopes it will speed discovery of new drugs, a process he finds painfully slow. “There’s a sense of urgency,” he said. “A lot of patients still need new treatments.”

Other vets are testing stem cell treatments on pets, as well as cutting-edge CAR-T cell therapy, which harnesses a patient’s own immune system to kill cancer cells. Kent has a new paper coming out soon on using a dog’s own natural killer cells, a type of blood cell, to attack osteosarcoma, a bone cancer that’s remarkably similar in humans and dogs.

At many of the nation’s top veterinary schools — and even at prestigious medical schools such as Stanford — veterinarians are working closely with M.D.s and Ph.D.s to further clinical research in a host of intractable diseases using a broad range of animals.

“The field is building momentum,” said Dr. Kathryn M. Meurs, associate dean at the North Carolina State College of Veterinary Medicine, which is part of a large Comparative Medicine Institute where veterinarians regularly collaborate with doctors at Duke University and the University of North Carolina. “It’s taking on more substantial problems like cancer, infectious disease, cardiology and neurology,” she said.

Meurs, a veterinary cardiologist, studies inherited cardiomyopathy and is trying to understand why members of the same family with the same inherited genetic defect can exhibit widely different manifestations of the disease. But it’s hard to tackle such a question in humans, who get the disease so late in life and usually have few siblings for comparison. So she uses dogs.

“Individual variation is much easier to study in an animal model that might have 10 offspring in one litter,” she said.

Companion animals offer numerous other benefits for medical researchers, she said. For example, pets are often exposed to the same disease-causing environmental factors as humans. (In fact, many veterinary schools refer to their work in comparative medicine as “One Health,” a philosophy that sees animal, human and environmental health as closely interconnected.)

Dogs and cats get cancer spontaneously, like humans, so their cancers are more biologically relevant to humans than the cancers that are artificially induced in lab animals. In some cancers, dog and human tumors are indistinguishable under a microscope. Surgical techniques can easily be adapted from dogs to humans, as they have been in limb-saving bone cancer surgery. And dogs are much closer in size to humans than are lab animals.

“We use the same diagnostics, the same treatment. These are all the same drugs and approaches we would use in people,” said Dr. Jessica Lawrence, an associate professor at the University of Minnesota Veterinary Medical Center, who said her colleagues at the University of Minnesota Medical School are often startled to learn how advanced the cancer care she offers her animal patients is.

No one is suggesting throwing mice and rats out of the lab. They’re pervasive in medical research because of their short lifespans and because they’re easy to keep and breed in captivity. Reliance on the rodents increased in the 1980s after transgenic technologies allowed scientists to alter the genes of mice and even insert human genes into the animals.

They’re still critical for understanding basic pathways and molecular targets, for example. But more than 90 percent of drug treatments tested in mice have failed to translate to humans.

“Mice and rats have been great, but they’re not always the right model,” said Dr. Megan Albertelli, a veterinarian and assistant professor in Stanford’s department of comparative medicine. “When you hit a wall, you’ve got to start looking for something new.”

Albertelli’s department works on a variety of animals, from transgenic mice to African clawed frogs; Albertelli is in the early phases of a project to investigate whether a tiny Madagascar primate, the mouse lemur, might be a useful new model for studying human disease. She notes that CRISPR gene-editing technology is likely to allow genetic manipulations in a wide range of animals not traditionally used in lab work.

She often sees raised eyebrows when she tells people she’s a vet who works at Stanford, which has no veterinary school. But Albertelli said she brings an important viewpoint to clinical research there.

“I’m always thinking about different species. How is an animal going to be similar [to humans] and how is it going to be different?” she said.

Vets have taken at least one page from human clinical research. They are starting to run larger and more sophisticated studies of new therapies.

When she started in the field about a decade ago, Lawrence focused solely on her animal patients. Better treatments for cancer in dogs are an urgent need; the disease kills some half of dogs over age 10. But as she’s encountered more and more people who have dealt with cancer, Lawrence has become increasingly interested in working to benefit humans as well.

The fact that canine clinical trials might help improve human cancer treatment also goes over well with pet owners. “Everyone knows someone with cancer,” she said.

But working with companion animals can be more challenging than studies of mice and rats. Care given as part of a clinical trial is not always completely free because vet schools have little of the hefty pharmaceutical industry funding that can help defray the cost of research. Animal patients often come with fiercely devoted pet owners who want to do anything to save the lives of their pets; the informed consent process is taken seriously, Kent said, so that pet owners understand all risks.

While Kent is excited about the potential of his research on cancer, he makes it clear that the subjects of his research are patients first.

“I’m not going to do anything to advance science at the cost of my patients. The first thing is do no harm,” said Kent, speaking in his office near a wall covered with dozens of photos his patients’ owners have given him over the years. “But if we can learn from them, and help them as well, that’s a really good goal. And if we can help humans as well, that’s great.”