September 11, 2012
Researchers Look To New Methods For Treating Cancer In Dogs
April Flowers for redOrbit.com - Your Universe Online
Two recent studies have shown real progress in killing cancer cells in dogs.The first study, from the University of Illinois at Urbana-Champaign, reports that myxoma, a pox virus that affects rabbits but not humans, dogs or other vertebrates studied so far, infects several different types of canine cancer cells in cell culture while sparing healthy cells. The study adds to the evidence that viruses or modified viruses will emerge as relatively benign cancer treatments to complement or replace standard cancer therapies.
Published in the American Journal of Veterinary Research, this study is unique in that it focused on spontaneously occurring cancers in dogs, allowing the researchers to avoid a common practice of testing viral therapies on mice or rats with induced human cancers. Such animals must be immunosuppressed to prevent their immune systems from rejecting the foreign tissue, complicating the results.
Pathobiology professor Amy MacNeill says that treating cancers with viruses could offer several advantages over standard cancer therapies. Many cancers have impaired anti-viral defenses, which allow viruses to target tumors while sparing healthy cells. Under the right conditions, infection with an oncolytic (cancer-killing) virus exterminates cancer cells and elicits an anti-cancer immune response without spurring a harmful inflammatory response. Chemotherapy and radiation, on the other hand, kill healthy cells along with cancer cells and radiation can cause abrupt cell death that spurs inflammation and pain.
"Ideally, what would happen is the virus would get into a few cancer cells, cause cell death and then spread to the other tumor cells nearby," she said.
Recent studies have shown that oncolytic viral therapies can be used successfully in conjunction with traditional approaches.
"There was a study in cats where they removed the tumor surgically and then they put a viral therapy in the area where the tumor had been removed," she said. The animals that received the viral therapy had significantly less regrowth of the cancer than those that weren't exposed to the virus after surgery.
"Other studies have shown that once you've eliminated a cancer with an oncolytic virus, if you re-challenge that animal with the same cancer cells, they don't develop tumors," MacNeill said. Viral infection of the cancer cells appears to train the immune system to better recognize the cancer.
In this new study, the team wanted to see if spontaneously occurring cancers in dogs were responsive to infection with a virus that is not a pathogen in humans or dogs. What they found was that cancerous and healthy canine cells respond as human cells do to myxoma infection. The virus invades cancer cells without affecting the healthy cells.
The study also showed that a version of the myxoma virus with a single gene deleted was four times more effective than the unaltered version. The deleted gene codes for a protein that hinders cell death in infected cells.
More testing is needed, and there are years of tests and trials ahead, but if all goes well, they will eventually test the virus in dogs with cancer.
"We wanted to make sure that the dog cells were like the human cells because we want to use these viruses not only to cure dogs of cancer but also to use the dogs as better models for humans with cancer," she said. "People are beginning to see the logic of this approach. These dogs have spontaneous tumors just like humans, they're living in the same environment as humans, they're exposed to the same carcinogens in the water if there are any and they sometimes even share our food."
She calls this approach a "win-win" for dogs and humans.
"This way we can test the therapy in dogs while at the same time treating them," she said. "Other researchers can take our results and use them to develop therapies for human patients."
The second study, conducted by the University of Pennsylvania School of Veterinary Medicine, treated dogs with a compound derived from a mushroom to extend their survival time.
This study, published in the open-access journal Evidence-Based Complementary and Alternative Medicine, reports that dogs treated with a compound derived from the Coriolus versicolor mushroom had the longest survival times ever reported for dogs with the disease. These promising findings offer hope that the compound may one day offer cancer patients – human and canine alike – a viable alternative or complementary treatment to traditional chemotherapies.
Commonly known as the Yunzhi mushroom, Coriolus versicolor has been used in traditional Chinese medicine for over 2,000 years. The compound in the mushroom that is believed to have immune-boosting properties is polysaccharopeptide, or PSP, which in the last two decades, has been suggested to have a tumor-fighting effect.
“There have been a series of studies looking at groups of people with cancer,” Dorothy Cimino Brown, director of the Veterinary Clinical Investigation Center, said. “The issue with those studies is that they weren´t necessarily measuring what most people would think is the most clinically important result, which is, do people taking PSP live longer?”
To address this question, the team tested the compound on dogs with naturally occurring hemangiosarcoma, an aggressive, invasive cancer that arises from the blood cells and typically affects the spleen. Most commonly, this cancer strikes at Golden Retrievers and German Shepherds.
A test group of 15 dogs diagnosed with hemangiosarcoma participated. They were divided into three groups of five, each group received a different dose (25, 50 or 100 milligrams/ kilograms per day) of I'm-Yunity, a formulation of PSP.
Owners were asked to give their dogs daily doses, then once a month the dogs were brought to Penn's Ryan Veterinary Hospital for follow-up visits where the researchers would take blood samples and conduct ultrasounds to track tumor growth and spread. Based on these criteria, the results suggest that the I'm-Yunity effectively fights the tumors.
“We were shocked,” Cimino Brown said. “Prior to this, the longest reported median survival time of dogs with hemangiosarcoma of the spleen that underwent no further treatment was 86 days. We had dogs that lived beyond a year with nothing other than this mushroom as treatment.”
There were not statistically significant differences in survival between the three dosage groups, though the median survival time was highest in the 100 mg group, at 199 days, eclipsing the previously reported median survival time.
The results were so startling to the researchers that they requested the Penn Vet pathologist recheck the dogs' tissue biopsies to be sure they really had the disease in the first place.
“They reread the samples and said, yes, it´s really hemangiosarcoma,” Cimino Brown said. Chemotherapy is available for treating hemangiosarcoma, but many owners opt not to pursue that treatment once their dog is diagnosed.
“It doesn´t hugely increase survival, it´s expensive and it means a lot of back and forth to the vet for the dog,” Cimino Brown said. “So you have to figure in quality of life.”
I'm-Yunity is not inexpensive, but it would offer owners a way of extending their pet's life without excessive trips to the vet. In addition, the team found no evidence of adverse effects from the PSP treatment.
They are gearing up for further trials of I'm-Yunity in dogs with hemangiosarcoma to confirm and refine their results. One trial will compare I'm-Yunity to a placebo and another will compare the compound to standard chemotherapy. Depending on the results, veterinarians could eventually prescribe the compound for treating this and other cancers, in dogs.
The company that manufactures I'm-Yunity may also pursue large-scale clinical trials in humans.
“Although hemangiosarcoma is a very sad and devastating disease,” Cimino Brown said, “in the long term, if we prove that this works, this treatment can be a really nice alternative for owners to have increased quality time with their pet at the end of its life.”