Studying cancer in pets benefits human patients, too

Photo of research at work Humans, as well as dogs, cats and horses, benefit from the research at the Center for Companion Animal Health.

The gleaming two-story building on the UC Davis campus looks like a typical medical clinic, but with subtle differences. The parking lot has a dog walk area, and in back there's a bucolic horse stable. Inside, portraits of bulldogs, kittens and goats adorn the walls. The suite where technicians administer radiation treatment has a dry-erase board listing scheduled appointments with Sheba, Sassy and Taco.

This state-of-the-art hospital is the Center for Companion Animal Health, where it's common to see a black lab sauntering down a hall or a Persian cat resting on a lap in the waiting room. People bring their sick pets here for life-extending treatments. What many don't realize is that these animals may in turn help extend human lives – particularly in the fight against cancer.

"Our goal is to do something mutually beneficial," says Professor Xinbin Chen, 45, who holds appointments at the UC Davis Cancer Center and the School of Veterinary Medicine. "We can help the companion animals and, meanwhile, use the animals to learn more about human cancer."

Chen joined UC Davis in March to establish and direct the new Veterinary Oncology Laboratory in the center. His work is an outgrowth of the Cancer Biology in Animals program, one of six core areas of emphasis at UC Davis' National Cancer Institute-designated cancer center. The program focuses on bridging the gap between human and animal medicine.

Chen and his team will conduct research that draws on UC Davis' rare combination of resources: the renowned cancer center and its School of Veterinary Medicine. That powerful collaboration gives the university one of the nation's leading comparative oncology programs, says Chen.

With graying hair and a quick smile, Chen moved west after serving as co-director of the University of Alabama Cancer Center's Tumor Biology Program. Although he began studying veterinary microbiology and clinical medicine in China, it was during his graduate study in the United States that he realized there were strong connections between cancers in people and domestic animals.

One such connection surfaced in the 1990s with the gene p53. The subject of thousands of research papers in that period, p53 is a gene encoding a protein that was found mutated in half of all human tumors. Given that, like humans, cats, dogs and horses also develop cancer, Chen wondered: Would mutant p53 be present in their tumors as well? A review of the sparse veterinary literature revealed the answer — yes — and Chen's fascination with the molecular similarities between animal and human cancers was born.

"Why are certain breeds of horses more susceptible to melanoma? This is veterinary medicine, but it may in the future apply to human melanoma."
— Xinbin Chen, researcher

Studying cancer in domestic animals makes good scientific sense, Chen says. Pets live in the same environment as people do, often sharing the air, water, food and sleep patterns of their owners. Like humans, these animals develop tumors that arise spontaneously, grow fairly slowly and are associated with old age. And dogs, cats and horses are more closely related genetically to humans than are the laboratory mice typically used in research.

"It's puzzling," the bespectacled Chen says with a chuckle. "Cancer in mice has been cured many times. But often the drugs that work in mice don't work in humans. We need some new animal models."

That's the idea behind comparative oncology, which UC Davis researchers began exploring many years ago. In the 1960s, for instance, scientists studied dogs in order to develop tumor radiation protocols for human patients. More recently, the UC Davis Cancer Biology in Animals program tested a range of new anti-cancer drugs in cats and dogs. Chen is now broadening the program to include horses and aims to focus studies on three kinds of cancer common in companion animals: melanoma, osteosarcoma and lymphoma.

To get the new program and laboratory up and running, Chen has been busy assembling and training a team of veterinarians to study and treat cancer in domestic animals. He also has hired a drug trial coordinator — the first ever for the veterinary school — to track data on how animal patients respond to experimental therapies. Ultimately, he hopes to learn more about the role of p53 and other genes in tumor growth and use that knowledge to develop more effective cancer treatments for people and their pets.

Already his team is testing a drug that might one day be deployed against non-Hodgkin's lymphoma, a cancer of the immune system that each year strikes about 60,000 Americans and kills 18,000. The compound is a small peptide that appears to inhibit the progression of the disease. Kit Lam, chief of the Division of Hematology and Oncology at the UC Davis Cancer Center, is now giving the promising drug to cats and dogs with lymphoma and collecting data on the results.

"When we use cats and dogs to test drugs — instead of lab mice — it's much more likely that they will work in humans," Chen says.

This advantage is not lost on drug companies, notes Chand Khanna, director of the comparative oncology program at the National Cancer Institute's Center for Cancer Research in Bethesda, Md. "New tools for studying cancer in companion animals are now helping us to find out why cancer goes away with some therapies and doesn't go away with others," he says. "That information is very valuable to the pharmaceutical industry."

The UC Davis program, he adds, will contribute research data to a national Comparative Oncology Trials Consortium made up of 14 university re-search centers. The consortium collaborates with the U.S. Food and Drug Administration and with pharmaceutical companies.

"The goal," Khanna explains, "is to learn more about new therapies and to use that information to develop the best human clinical trials possible."

Chen's particular interest is to find new drugs that can be used in combination with radiation therapy to prevent metastasis — the spread of cancer throughout the body. That's what kills patients with osteosarcoma, a bone cancer that is the second major cancer in children, and also is common in dogs. Chen is testing compounds that bind to mutant p53 and can restore its normal function as a tumor suppressor.

"If this works well in dogs, then maybe we'll have better justification to try it in kids," he says.

In the longer term, the UC Davis program on compar-ative oncology could yield entirely new approaches for treating these three cancers, as clues reveal discoveries about other key genes besides p53. Chen already sees a golden opportunity to learn more about melanoma — the most lethal form of skin cancer — by studying the genetics of the disease in horses.

"Why are certain breeds of horses more susceptible to melanoma?" Chen asks. "This is veterinary medicine, but it may in the future apply to human melanoma."

Because horses tend to be inbred, their pool of genes shows limited variety.

Information about their breeding is also readily available. By examining DNA from horses with and without melanoma, Chen hopes to find new genes associated with the disease. Then, he'll search the human genome for comparable genes and investigate whether these might be good targets for new kinds of melanoma treatments.

In the meantime, animal patients should benefit from the research, as Chen's team tries some of the latest therapies for humans on ailing pets. Animals with melanoma and osteosarcoma, for example, will be given an antibody-based treatment to see if the drug helps prevent metastasis, as it does in cases of human breast cancer.

"We may not be able to cure someone's pet now, but in the future someone else's pets will get better care," says Chen. And there's an indirect benefit, too. "When a pet lives longer, it increases the owner's lifespan," he notes. "Animal health is part of human health."