Intercepting Cancer Signals

What is Canine Melanoma? 

Canine melanoma is a type of cancerous tumour that affects dogs. These tumours are typically found in a dog’s mouth or nail beds but can appear anywhere on their body. It is a fairly common diagnosis, and many dogs are referred to the OVC Mona Campbell Centre for Animal Cancer each year to undergo specialized treatment. However, this cancer can spread very quickly, making it hard for veterinarians to treat. 

To tackle this pressing issue, a research team led by Dr. Anthony Mutsaers, veterinary oncologist, cancer researcher and associate professor at OVC, is studying this disease on a cellular level. His team’s goal is to improve treatment outcomes and extend the life expectancy of dogs diagnosed with melanoma. 

“When people hear the word, ‘melanoma,’ the first thing that usually comes to mind is the type of skin cancer that people get from the sun, but dogs can get it too,” says Mutsaers. “It’s actually one of the most frequent causes of canine malignant oral tumours.” 

In humans, melanoma is most often caused by sun damage and ultraviolet (UV) exposure, but this is not the case in dogs. The cause of canine melanoma is largely unknown — although the risk is higher in older dogs and among certain breeds, such as black labradors and chow chows.  

The Problem: Canine Melanoma Can Easily Dodge Cancer Treatments 

Human melanoma is highly curable if caught and treated early; however, canine melanoma is often diagnosed at a later stage, and behaves aggressively. This cancer can spread quickly into a dog’s lymph nodes, lungs and elsewhere, which makes treatments like chemotherapy (“chemo”), vaccination, radiation or surgery less effective. While all of these treatments may extend the lifespan of a dog with melanoma, this cancer is highly invasive, and survival rates are often low.  

“Canine melanoma is notoriously very hard to treat because of how fast it spreads, and how resistant it is to chemo options,” says Mutsaers. “Even when veterinarians use a combination of treatments, the prognosis for canine melanoma is generally poor.” 

Current treatment options target and kill rapidly dividing cancer cells, but they do not get to the root cause of the issue. In contrast, Mutsaers’ team is researching ways to prevent the tumour cells from growing and spreading, by using drugs that block cell signalling pathways.  

How Do Cells Communicate?  

Signalling pathways are a series of proteins inside the cell that help them communicate and function. Proteins on different parts of the cell called ‘receptors’ receive messages from other cells, or the environment, that tell the cell what to do. Once “turned on” by these messages, the signalling pathways start a series of chemical reactions within the cell, which are vital for cell growth and survival.  

“I like to think of cell signalling pathways as an hourglass,” says Mutsaers. “You have lots of different inputs from the environment that bind to receptors on the cell. Then, these inputs get funneled through a narrow pathway and the result is a wide range of different outputs.” 

In healthy tissues, these pathways are very important for normal function—for example, signalling pathways that instruct cells to repair themselves after an injury. But in cancer tumours, the pathways are ‘upregulated’, which means that they are working in excess, allowing cancer cells to divide, grow, thrive and spread faster than cells in healthy tissues.  

“Since canine melanoma resists chemotherapy, we want to try to block the pathways that help the tumour grow and survive,” says Mutsaers. “My lab is researching this concept to better understand these cancer pathways and improve the way melanoma is treated.” 

The Solution: Fighting Canine Melanoma Pathways Within the Cell 

A core pathway in canine melanoma tumour spread is called ‘mTOR/PI3K’; Mutsaers’ research team has been studying the impact of a drug treatment that blocks this pathway on cancer cell growth. In a recent lab study, they treated canine melanoma tumour cells with a combination of the common chemo drug, carboplatin, and an mTOR/PI3K inhibitor drug.  

“Carboplatin is the go-to chemo drug for melanoma cases in veterinary practice,” says Mutsaers. “We wanted to see if combining it with an mTOR/PI3K inhibitor drug would have any impact on the number of cancer cells that chemotherapy would kill on its own.”