Researching cancer in pets and people to develop better therapies for both
When Krysia Lamore first brought Carmelito to the UC Davis School of Veterinary Medicine for enrollment in a clinical trial, the inoperable tumor inside the orange and white cat's mouth was the size of a plum.
If the trial's two-drug combination looked promising in cats, says veterinarian Katherine Skorupski, researchers would begin using the same therapy in human clinical trials for head and neck cancer.
"Katherine outlined the risks involved, but I never considered not enrolling Carmelito," Lamore says. "That research was going to benefit people in the long run as well as animals, so I knew how important it was."
Lamore voices the heart of the program behind Skorupski's efforts: UC Davis Cancer Center's comparative oncology program. A collaboration between the School of Veterinary Medicine and the School of Medicine, the program supports researchers who are developing therapies for lymphoma and osteosarcoma that strike humans and companion animals alike.
Of pets and people
Advantages to working with companion animals to develop new cancer therapies are numerous, says Xinbin Chen, a veterinary oncologist who came to UC Davis in 2007 to direct the comparative oncology program.
"These animals live with people in their homes or — like horses — close by. They share our environment," he says. "So when we study their naturally occurring cancers, we're working with a model that is very close to humans."
"If we can work out the science of why one dog responds and one does not, then we can relate that back to human tumors."
— Ralph deVere White, UC Davis Cancer Center director
Companion animals are genetically much closer to humans than the highly inbred mice and rats commonly used in cancer research, Chen says. And, like human cancers, cancers that occur in dogs and cats are often slow growing and associated with age.
"From a medical research point, the dog has a unique advantage because its physiology is similar to ours, so toxicity studies in dogs often can apply directly to people," says Chen.
As one of the few universities that houses both a world-class veterinary school and a National Cancer Institute-designated cancer center, UC Davis is the perfect home for the program, says cancer center director Ralph deVere White.
"What we're doing here is tremendously exciting on so many levels," he says. "For example, we can take a new drug that looks promising in a mouse model or in human cell lines, and instead of doing phase I and II trials in human cancer patients, we can run the studies in our companion animals at the vet school. We give the animals the very best therapy, and then we can bring that therapy to humans."
A professor of urology, deVere White has been doing just that. In 2007, he led a team that found that an extract cultured from soybeans and mushrooms, called GCP, had striking cytotoxic effects against prostate cancer cells. Phil Mack, a cancer center research geneticist, found similar effects in canine and human lymphoma cell lines.
Following those discoveries, a GCP trial was initiated in 12 canine lymphoma patients. One finding from this ongoing study is that absorption of the extract is highly variable.
This is the kind of valuable information that can be obtained from comparative oncology, says deVere White.
"If we can work out the science of why one dog responds and one does not, then we can relate that back to human tumors," deVere White says.
Quality of life
Osteosarcoma is a bone cancer that strikes up to 10,000 canines annually in the U.S. and some 900 humans, nearly half of whom are children and adolescents younger than 20 years old. Because it quickly metastasizes to the lungs, surgery and chemotherapy are the standards of care for both people and pets.
While cure rates are nearly 70 percent for people who have no detectable metastases at diagnosis, only one of four dogs is still alive two years after treatment.
For the past year, veterinarian Carlos O. Rodriguez Jr. has been enrolling dogs in a trial to test whether a drug called gemcitabine, when administered as a breathable mist, can control lung metastasis in osteosarcoma. Previous work has shown that such a mist kills the cancer cells in the lungs of mice.
"If we can deliver the drug by inhalant therapy instead of intravenously," he says, "we can use much less of it while delivering a relatively higher dose to the lungs, which are the affected organ."
So far the results of the trial look promising. Rodriguez's canine patients have not suffered any serious side effects, and their owners have had little trouble administering the drug at home using nebulizers and masks.
"We haven't finished evaluating the pathology," Rodriguez adds, "but we've found lakes of necrosis where the lung metastases have been killed by the treatment."
If the treatment proves effective, he says, not only will it prolong the life of dogs with osteosarcoma while sparing them from the side effects of chemotherapy, it will also provide the kind of information researchers need to initiate similar studies in children.
When Carmelito showed up in Katherine Skorupski's clinic in July 2007, he was clearly a good candidate for her squamous cell carcinoma trial. The average survival for a cat that presents with the disease is only two months regardless of treatment.
Skorupski, an assistant professor of clinical medical oncology in the School of Veterinary Medicine, was testing a combination of two new drugs that starve cancer cells of polyamines, growth factors required for cell proliferation.
She found Carmelito to be the perfect patient.
"He's a cat with a really good attitude," she says fondly. He readily accepted the fishflavored medicine he was fed from a syringe twice a day.
By the second visit, it was clear to Skorupski that the fluffy cat's tumor was considerably smaller.
"I remember going to get a colleague and saying ‘Look at this and measure it for me,' because I didn't believe what I was seeing," she says.
Although 12 of the 13 cats in the trial eventually died, seven of them experienced a period of tumor shrinkage or stabilization. Based on the trial, Skorupski says, her collaborators in Pennsylvania are hoping to start human clinical trials soon.
Mid-April, when the magazine went to print, Carmelito was still alive.
"When we started this study, I thought that he might last a month. Then he went two months, then three. Then he just kept going," says owner Lamore, who encourages others to put their pets into UC Davis' comparative oncology trials.
"It's been nothing but an extremely positive experience for me and the cat," she states emphatically. " And it can only further help animals and people."