A University of Calgary physician has identified how cancer spreads in the brain in a study published Tuesday in the journal PLoS Biology.

Oncology Prof. Peter Forsyth and his team pinpointed the molecular "switch" that signals cancer cells to migrate away from the primary tumour site.

"Brain cancers are a very deadly disease. The average patient only lives about a year with the best available treatments with radiation, with chemotherapy and surgery, so clearly we have to do a much better job," said Forsyth, the study's author.

The "switch" is a molecule called the p75 neurotrophin receptor. It is mainly found in embryonic brain development where it acts as a brake, stopping brain cells from migrating and growing.

But cancer cells exploit this mechanism to accelerate their growth and invade healthy brain tissue.

"[They've] sort of turned the normal machinery to the dark side of the force and used it for their own benefit," he said.

Malignant glioma is an aggressive cancer of the support cells — or glia — of the brain that represents approximately half of all brain cancers.

Forsyth used an experimental model of human malignant glioma implanted in the brains of mice. His team was able to track the spread of the cancer from the main tumour body, along vine-like processes called "tendrils" that projected to other parts of the brain.

"As [the tendrils] move into the brain they don't cause much trouble initially. It's when they get to their destination and set up shop that they start to cause damage," said Forsyth.

These tendrils render surgical removal of a brain tumour ineffective in 95 per cent of cases, because the cancer simply re-establishes in another part of the brain. Additionally, few chemotherapeutic drugs can cross a membrane barrier that protects the brain from blood-borne contaminants.

Combined, these properties make malignant glioma one of the most aggressive and lethal cancers.

Living with uncertainty

The recurrence of tumours and ineffectiveness of conventional therapy leaves brain cancer sufferers with few options. In more aggressive cancers, patient survival is typically less than a year.

Nazira Mamdani was one of the lucky ones. She was diagnosed with brain cancer in November 2004. The tumour was surgically removed in February 2005, but came back within a year. She's now cancer-free, but only following a year of difficult chemotherapy.

"Now that I'm done, it's very difficult to say what's going to happen next," she said. "You never know for sure."

For Mamdani and the many others with her condition, the future will always hold this uncertainty.

Forsyth wants to remove this uncertainty. Brain cancer thrives by hijacking healthy cellular machinery and using that machinery for its own benefit, he said.

"These tricky cancer cells, that would do anything to survive, have turned this brake into an accelerator. So they actually use part of the normal machinery a nerve cells use to stop growing, and they've turned it around and used it to grow and invade into the normal brain."

The p75 neurotrophin receptor is activated by a signalling molecule called BDNF or Brain Derived Neurotrophic Factor. BDNF is widely used by the brain. It supports the survival of neurons, as well as promoting new neurons and synaptic connections.

"They're [cancer cells] sort of turning the environment, the normal environment and the normal machinery to their own cause," said Forsyth.

Cancerous tendrils also exploit the brain's innate defence mechanisms to survive. "They turn on a lot of survival signals and resistance signals … and that's why we think they're a disease reservoir," he said.

Identifying therapeutic targets

By understanding how cancer hijacks the brain, scientists can learn how to interfere with it.

"If we could understand the switches that allow [migration] to occur and keep cancers as lumps, maybe they could just be taken out surgically and cured and we could close the cancer clinics, or at least reduce their size."

Forsyth and his research team will now take their findings back to the lab, where they will investigate different pharmaceutical strategies to figure out the best way to block the p75 receptor.

Although he's very excited about this discovery, Forsyth cautioned that it could take time before this "switch" can be turned off in a clinical setting.

"The important message for us is that we've made a discovery and we're working back towards the clinic rather than remaining isolated in our lab working on our individual proteins. Is it frustrating for patients and families? Of course. But you know we really need to develop the strong foundation and make discoveries and then move forward in a proper fashion, and unfortunately that takes time.

"I want it to be tomorrow."