Metformin is an anti-diabetic drug that's commonly used to treat Type 2 diabetes. The drug induces a protein in the cells which is responsive to stress and helps to potentially clean up damaged cells.
"If it finds a cell with damaged DNA, it essentially makes a decision to fix the damage or get rid of the cell. We know that it can stop the growth of normal cancer cells and drug-resistant cancer cells," explains Harkness, a professor in the medical college's Department of Anatomy and Cell Biology.
MacDonald, a veterinary medical oncologist, and Gaunt, a specialist in small animal internal medicine with an interest in endocrinology and diabetes, met Harkness after they heard that he was interested in testing metformin using an animal model.
"I sent an email saying, ‘Hey, we're over here at the veterinary college, and we're interested in becoming involved,'" says MacDonald.
That simple message led to an exciting collaboration that promises to have a significant impact on the treatment protocol for canine lymphoma while providing critical information that can benefit human cancer patients.
"The lymphomas that dogs get are very similar to human lymphomas, and they're actually treated with the same drugs," says Harkness. "They're a perfect model for human cancers, and we'll be able to get results much faster than with human trials."
With preliminary funding from the U of S College of Medicine and the WCVM, the researchers hope to begin treating canine lymphoma patients with metformin early in 2013. To gather enough patients that fit the study's requirements, they're asking local veterinarians to refer dogs that have already received chemotherapy treatment but have developed resistance to the drugs.
"These dogs are relatively rare because they respond quite well to the original treatment," explains Harkness. "They are the most serious cases, and if the drug works for them, then it may be used to treat all dogs when they come in with canine lymphoma."
Canine patients enrolled in the study will receive metformin as part of their cancer therapy regime at the WCVM. During their therapy, Harkness and his team will analyze tissue samples from the dogs to see if the results are similar to those they've seen at a cellular level.
Having everyone at the same campus is a huge advantage since the researchers can easily get together to discuss the trial, and the treated animals are close by. Harkness is also hopeful that dog owners will be more willing to include their animals in a local study.
"I think it gives confidence to the public that this is all local work. These are all local people working with local animals, and they're easily accessible to the dog owners if they want to talk to them and ask questions."
MacDonald and the oncology team at the WCVM's Veterinary Medical Centre are experienced in treating all types of cancer — particularly canine lymphoma, which is one of the most common types that they see.
Standard treatment for canine lymphoma involves a chemotherapy regimen, a multiple-drug protocol that includes 16 treatments over a period of 19 weeks. In order to ensure that the dogs maintain a good quality of life during and after treatment, doses are relatively low when compared to human chemotherapy protocols.
"The doses we use are effective, but our intent is not to make them sick," explains MacDonald. "We know that we're not going to cure them of the disease, but we can keep it in remission for a period of time."
Unfortunately, when canine lymphoma comes out of remission, the cancer cells are often resistant to the drugs used during the initial five-month chemotherapy protocol. For that reason, a second course of chemotherapy includes less-effective drugs that may cause more side effects. From the time of diagnosis, a dog's median survival time is one year.
Both MacDonald and Gaunt are optimistic that metformin could help to add time to their patients' lives by killing the drug-resistant cells and making it possible to reuse the initial drug protocol. Since drug resistance is a problem with all kinds of tumours, future research could include other types of cancer as well.
"If we can prove that it works, then maybe we can expand into a larger study to see if we can have an effect on a larger scale, and we could potentially work with other cancers besides lymphoma in the future," says Gaunt. "We're hoping that we can help our patients that we care about on a daily basis, and maybe we can have a major impact on their owners as well."
Harkness hopes that this study can lead to future collaborations with medical oncologists who are willing to treat their human patients by applying the knowledge that's been acquired from the lab and from the animal patients.
Excited by the possibilities, Harkness is grateful that MacDonald and Gaunt decided to send him that first email. "This research seems to be really applicable, and it's something that can benefit both animals and people. It has the potential to move things faster so that going from bench to bedside might be a lot quicker."