Targeting cells that harm

Vessels and the spread of cancer

As a young boy growing up in Ottawa, Jeffrey Wigle dreamed of becoming a fighter pilot – a dream prompted, perhaps, by one too many viewings of Top Gun.

While today his feet are firmly planted on the ground, you could say that Dr. Wigle’s work requires the same precision that Tom Cruise’s pilot character needed in the iconic 1986 film. Maybe more.

Dr. Wigle’s target? Cancer. The weapon? Research.

Specifically, Dr. Wigle’s research looks at blood vessels and lymphatic vessels.

“Everybody knows about blood vessels,” says Dr. Wigle, Principal Investigator, Vascular Development, Institute of Cardiovascular Sciences. “Those are the arteries and veins in the body. After a heart attack, you need to grow new blood vessels to get into the heart so that it’s more functional. We’re looking at ways to promote the growth of these blood vessels in that case.”

With cancer, the objective is the opposite.

“If a cancer is growing in the body, it needs to get more blood so it can grow bigger,” explains Wigle, who has been at St. Boniface Research since 2001. “To try to stop that, a new approach to treat cancer is to block the growth of these blood vessels and that’s what we’re looking at.”

Lymphatic vessels

While blood vessels are comparatively easy to grasp, lymphatic vessels are much less understood by the public. These vessels are easy to penetrate, and cells pass through them without effort. We need lymphatic vessels to allow white blood cells to move around to fight infection.

But when cancer strikes, says Dr. Wigle, it hijacks these vessels allowing tumour cells to penetrate and then spread the cancer around the body. The goal of the research conducted by Dr. Wigle and his lab personnel is to find a way to halt the spread of cancer by inhibiting the growth of the blood vessels and the lymphatic vessels, thereby cancelling the travel plans of the cancer cells.

The key, says Wigle, might lie in a gene called Prox1 which he describes as a “genetic switch.”

“Without this gene, lymphatics will not grow. We’re looking at how this gene works and the idea is that we can then devise better ways to block lymphatic growth in order to prevent cancer from spreading,” he explains.

This is where the Top Gun precision comes into play. The goal of this research, which is still in its early stages, is to shoot down only those problematic cells and to make sure the healthy cells do not become victims of friendly fire.

“A lot of the anti-cancer drugs that we have right now are essentially sledge hammers – they’ll go and they’ll hit any cell that divides.”

Sledge hammers

“When patients get treated for cancer with chemotherapy drugs, it hurts, it kills cells that divide. Cancer is unique in our bodies because it’s always actively growing, it has no off switch, it constantly grows. So a lot of the drugs that we have right now are essentially sledge hammers – they’ll go and they’ll hit any cell that divides,” Dr. Wigle explains. “That means these drugs will target normal cells in your body that divide a lot like hair cells, so people often lose their hair after cancer therapy, they also may have problems with their gut because their gut cells are always growing as well. An anti-cancer drug doesn’t only hit the tumour, it hits all these other components. What we’re looking to do is find better ways to prevent the cancer from spreading and make the treatment more specific for the cancer and not to hit the normal tissue.”

Dr. Wigle envisions a future where we will design therapies that target cancer better coupled with drugs that will prevent the cancer cells from dividing in the first place. “We’ll have new drugs that prevent lymphatic vessels and tumour blood vessels from growing, so we can hit the cancer in three different ways. We can prevent it from growing with new drugs; we can prevent it from spreading, either by spreading through the lymphatic vessels or the blood vessels and by stopping the blood vessels growing; we can starve the tumour of food and energy and then it won’t be able to grow.”

True success in cancer treatment can be achieved only through collaboration, says Dr. Wigle. While St. Boniface is unique with its expertise in lymphatics, there are other pieces of the puzzle such as developing a better understanding of the nature of tumour cells themselves.

Says Dr. Wigle: “To address the big questions in science nowadays, one person can’t do it alone.”

To learn more about Dr. Wigle’s research visit: sbrc.ca/wigle

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