Hand planting bulbs
Cancer stem cells, which enable some tumours to return after treatment, are like the bulbs of perennial plants. As long as the bulb is present, the plant will grow back. (Photo: iStock)

A UHN study has revealed a new therapeutic approach that could help to treat glioblastoma, the most common and most aggressive form of brain cancer in adults.

In 2017, glioblastoma claimed the life of Gord Downie, the frontman of iconic Canadian rock band, The Tragically Hip.

Glioblastoma is a deadly cancer diagnosed in approximately 1,000 Canadians every year. Less than five per cent of these individuals survive more than five years.

The rates of survival are dismal because most of these brain tumours do not respond to current treatments. New and more effective treatments are therefore urgently needed for this disease.

In the study, Dr. Valerie Wallace, a Senior Scientist at the Krembil Research Institute, and her trainee, Dr. Ahmed El-Sehemy, discovered that the protein Norrin plays an important role – albeit a complicated one – in the growth and proliferation of glioblastoma tumours.

"Norrin has been implicated in blood vessel formation in the brain, eye and inner ear, and the regulation of brain cell behaviour," Dr. Wallace says. "Our findings indicate that Norrin is present in a wide range of brain tumours and that higher levels of the protein are linked to better patient survival."

Glioblastoma tumours contain a small number of specialized cells known as cancer stem cells, which can give rise to new tumour cells. These stem cells are widely believed to be responsible for the cancer's resistance to treatment and its recurrence. Accordingly, targeting these cells could be the key to treating glioblastoma.

The researchers found that Norrin affects the growth and proliferation of a tumour's cancer stem cells.

In stem cells with high levels of the ASCL1 protein, Norrin promoted cell growth, whereas in cells with low ASCL1 levels, Norrin inhibited growth. Although ASCL1's role in brain cancer is not entirely clear yet, the protein is known to be involved in the generation of brain cells during development.

"Our study reveals an unanticipated role of Norrin in brain cancer progression," Dr. Wallace says. "Norrin could be a potential therapeutic target for glioblastoma tumours and may inform the design of patient-specific treatments."

This work was supported by the Cancer Research Society, the Canadian Institutes of Health Research and the Toronto General & Western Hospital Foundation. Dr. Wallace holds a Tier 1 Canada Research Chair in Retina Regeneration.

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