Toronto, ON – A multidisciplinary University of Saskatchewan research team will treat dogs with drug-resistant lymphoma to uncover the reasons for this resistance and to identify ways to reverse it. Although scientists have identified the various processes involved in anticancer drug resistance, it remains a major problem and effective treatment is lacking. The study recently received a $165,000 Innovation Grant from the Canadian Cancer Society.
“The cancer we’re studying – lymphoma – is very similar to human non-Hodgkin lymphoma. It’s spontaneous and responds to drug therapy. The same therapies are used, and both the canine and human cancers develop similar drug resistance,” says Dr Troy Harkness, who is study leader and a molecular geneticist and professor at the university. “Because dogs age faster than humans, their disease advances more quickly and we are able to observe results that much sooner.”
The dogs participating in the study have already been diagnosed with drug-resistant lymphoma. They will receive treatment on an outpatient basis and the results of their treatment will be analyzed as part of this study.
For over a decade, Dr Harkness’ research has focused primarily on cancers that no longer respond to treatment. Last year his research team began studying the effect of Metformin on dogs with drug-resistant lymphoma. Metformin is a drug that has long been used to treat type 2 diabetes. Metformin is thought to have anti-cancer properties, potentially by decreasing the risk of cancer and may also have an impact on existing cancers.
In this study, the researchers will combine Metformin with standard chemotherapy to test if this will re-sensitize the dogs to anticancer drugs. To unravel how the drug is affecting cancer, the researchers will identify molecular markers of drug resistance, test whether Metformin can return these markers to normal, and build a database of the genetic changes associated with the onset of canine lymphoma. The Saskatchewan researchers are the first in the world to look at how Metformin may work to reverse lymphoma drug resistance in dogs.
The canine patients are being cared for by a team of veterinarians (Drs Val MacDonald and Casey Gaunt at the Western College of Veterinary Medicine). The team of scientists also includes experts in medical endocrinology (Dr Terra Arnason) and bioinformatics (Dr Tony Kusalik). The multidisciplinary team is essential to understanding the genetic activity – which genes are turned on or off – and identifying potential targets for new drug treatments.
“Whatever we find in dogs, we predict will be similar in humans. If we find the right combination, we may be able to predict earlier when multiple drug resistance is happening, target these individuals and start with a new treatment that may ultimately be more effective,” says Dr Harkness.
The team should collect enough data within 2 years to have a good idea whether Metformin assists in reversing drug resistance. Then a similar study could be run with people to apply what the team has learned in dogs.
A video about Dr Harkness’ research can be viewed here.