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Tuesday, September 28, 2021

Finding the cure through household pets

YASH NAGDA / AGGIE
YASH NAGDA / AGGIE

UC Davis physicians and veterinarians collaborate in the Comparative Oncology Program to find a cure for cancer

Known as man’s best friend, dogs provide their owners with unconditional companionship, love and loyalty. And just as humans can learn a lot of things from a dog’s behavior and personality, they can also learn a lot from a dog’s immune system.

At UC Davis, physicians and veterinarians teamed up in the Comparative Oncology Program to conduct research on dogs with cancer. They then applied their research and findings to cancer in humans.

“What we’re looking at is what we can learn about from companion animals, particularly dogs and cats with cancer, and how it relates to cancer in humans,” said Michael Kent, a researcher, professor of surgical and radiological sciences and director of the Center for Companion Animal Health at UC Davis.

Although the team is just beginning their research with mice as the subject, there is more to be learned from cancer in many other species.

“[Being] the top vet school in the country, [UC Davis] obviously has access to these other potential models for learning about cancer,” said Arta Monjazeb, a professor of radiation oncology at the Comprehensive Cancer Center. “The comparative oncology and comparative pathology programs try to take advantage of that in really being able to compare cancer and compare pathology across species, and find the common ground to find models of disease that better represent human disease.”

The research is a two-way street both those dealing with veterinary medicine and with human medicine are able to learn from each other’s findings.

“It’s kind of a win-win situation in the way we get to learn more and study [what] we otherwise wouldn’t be able to do,” Monjazeb said. “[Veterinary researchers] get access to medicines and new cutting-edge techniques […] that really aren’t generally being developed for veterinary oncology.”

Before trying out a new therapy or treatment, the physicians and veterinarians must go through a research review board to ensure everything meets ethical standards. The review board also assures, that there is reasonable expectation, that there will not be any injuries and that there will be some sort of response from the treatment. Animal owners are then presented with all the treatment options to decide if they would like to participate in a clinical trial. From there, the clinical trial is conducted in order to develop a treatment or therapy.

Monjazeb’s focus, in collaboration with other veterinarians and physicians, is on understanding how the human immune system combats cancer. He and his team are trying to find ways to reinvigorate the immune system to help fight cancer.

“The idea is that cancers are mutated parts of our body so they express abnormal proteins,” Monjazeb said. “Our bodies should be able to recognize these abnormal proteins and kill the cancer cells the same way that they would kill a cell infected with a virus, because it would be expressing abnormal proteins. But in reality, what happens is the cancer develops very intricate ways to actually trick the immune system and kind of escape.”

Dogs are commonly used for research because their immune systems and cancers are similar to humans’. Like humans, cancer in dogs is known to develop spontaneously.

“The mouse models that we use are very artificial models; they’re all inbred,” Monjazeb said. “Their immune systems don’t necessarily closely reflect the way that the human immune system works, and the cancers that we give to these mice are definitely nothing like human cancers. The cancers are grown in petri dishes and injected into mice and used for studies.”

Some of the current clinical trials include identifying lymph node metastasis, assessing ventricular arrhythmias during treatment for lymphoma, evaluating a diagnostic tool for large bowel disease in dogs, assessing a new addition to treatment of canine osteosarcoma and assessing an immunotherapy in canine osteosarcoma.

In particular, this assessment is a new addition to the treatment of canine osteosarcoma, and involves 19 other veterinary schools and approximately 160 dogs nationwide.

“It’s evaluating whether an oral medication called Rapamycin can help improve outcomes for dog with osteosarcoma,” said Jenna Burton, assistant professor of clinical medical oncology at the UC Davis School of Veterinary Medicine.

Burton is also working on a clinical trial of a new formulation of doxorubicin, a drug that is widely used to treat lymphoma and other cancers in humans.

“We’re giving that drug to dogs with lymphoma to get some more information about it,” Burton said. “[Such as its] safety, its tolerability, how well it works and whether we can potentially reduce some of the common side effects that we see with doxorubicin, namely toxicity to the heart.”

Kent said that one of the major challenges overall is dealing with cancer and its ever-changing form.

“Cancer is tough,” Kent said. “It’s not one disease. Cancer is thousands of different diseases and not to anthropomorphize cancer, but cancer is really smart. It almost works in a Darwinian way. You kill a batch of the cells this way and they develop new ways to get around it and they get resistant to treatment.”

According to Kent, the research has not really been a challenge in terms of working with their physicians.

“It’s been great working with the medical school,” Kent said. “And there are some differences between the species but not that much. I’d say our biggest challenge is the fight against cancer. You have to be in it for the long haul.”

Butron also pointed out the fine line between people’s perception of animal research and actually conducting  clinical trials in companion animals. She said that since dogs and cats are “people’s animals,” it is really important that they are treated as someone’s pet and not as a research subject.

“We never lose sight of the fact that these are someone’s family members,” Burton said. “I think part of the challenge is communicating our message that clinical trials in dogs and cats ultimately are designed to help our pets and help us answer questions about ways that we can treat cancer more effectively with less side effects.”

Kent reiterated Burton’s point, while also pointing out the importance of the Hippocratic Oath: “first do no harm”.

“It’s really important to realize that we’re dealing with someone’s beloved pet,” Kent said. “These are not lab animals and we have to make sure we do things in an ethical way, but also it’s really important to realize the promise of using these kind of patients that we have in a way that can help other dogs and then down the road, that will hopefully help people too.”

Written by: Jacqueline Chu – features@theaggie.org

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