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Simple virus may fight deadly brain cancer


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TORONTO (CP) -- A common virus that poses no threat to humans may be a magic bullet in the fight against one of the most deadly forms of cancer.

Researchers from Calgary have found that something called a reovirus appears to destroy tumours in glioma, the most virulent of brain cancers.

The findings were reported Wednesday in a prominent American publication, the Journal of the National Cancer Institute.

Lead author Dr. Peter Forsyth said his team hopes to begin human clinical trials in about six months.

"It's fast," he said Tuesday from Calgary. "That's part of what makes it exciting."

He cautioned, however, that it could be several years before it will be a treatment option outside of clinical trials.

Malignant gliomas are highly aggressive, invasive and resistant to conventional treatments. The average survival from diagnosis is one year. Long-term survival is rare. And despite the fact that treatment of other cancers has progressed exponentially over the last 20 years, little ground has been gained in the fight against glioma.

Scientists around the world have been studying whether these and other cancers can be stopped by viruses, working with a variety including herpes simplex, poliovirus and the measles virus. (The poliovirus is genetically modified so it can no longer cause poliomyelitis.)

"It's just exciting that people are exploring this new area. And the results are very, very impressive -- with this virus and a number of others," said Forsyth, a neuro-oncologist at the University of Calgary and at the city's Tom Baker Cancer Centre.

He is particularly excited about the potential of reovirus, which unlike some of the other candidates, does not cause disease in humans.

"Chances are if you have kids or when you were a kid you picked it up in day care and it's going to give you a runny nose and diarrhea and that's it," he said.

"So it doesn't cause disease and it does not cause harm."

Another exciting feature of reovirus is that it appears to be able to kill not only the tumour cells in the initial cancer site, but tumour cells which have developed elsewhere. That's important for battling glioma, because the cancer sends out finger-like tumours throughout the brain, making surgical removal impossible.

To date the treatment has been tested in human cell lines (a small collection of tumour cells grown in vitro), in mice and in glioma tumour fragments removed from patients' brains. In the cell cultures, reovirus killed 20 of 24 cell lines.

The treatment was equally effective in mice. After a single injection of reovirus into the tumours, nine of 11 were alive and thriving after 90 days. None of the mice in a control group -- which were injected with dead reovirus -- were alive at 90 days.

"It prolongs survival dramatically," Forsyth said.

"It looks like most of the mice are probably cured of their tumour. And when you look in the brains and cut them up, you really don't see any big lumps or hunks of tumour. It looks like it's all gone."

While Forsyth's research is likely to spark excitement, some in the field are urging caution.

Dr. Matthias Gromeier, who leads the research into the use of poliovirus as a cancer fighting agent, believes more study must be done to determine a virus's impact on healthy tissue as well as tumour cells.

He made the comment in an editorial published by the journal.

"There is justifiable concern that intracerebral (into the brain ) inoculation of reovirus preparations in humans may either unleash unknown properties of these agents or provide a suitable milieu promoting adaptation events that give rise to altered pathogens with new properties," said Gromeier, a professor of microbiology at Duke University in Durham, N.C.

The next phase of Forsyth's research is to inject the reovirus into the brains of healthy primates, probably monkeys, to ensure it does not produce such unanticipated and unwanted side-effects.

If it proves to be safe, it will be administered in the same way in humans -- a hole will be bored into the head and the virus will be injected into the tumour.

Forsyth said virus therapy may push cancer treatment into new realms.

"We've gone probably about as far as we can go with conventional treatment, in terms of cancer therapy in general. In terms of surgery, radiation or chemotherapy. Those things have been pushed as far as they can go, probably.

"And patients -- and everybody else -- are a little bit frustrated by that. So this is a new way of thinking about treating cancer," he said.

His research was funded by the National Cancer Institute of Canada, the Alberta Cancer Board, Partners in Health, the Brain Tumor Foundation of Canada, the Dr. Michael Longinotto Molecular Neuro-Oncology Fellowship Fund and Clark Smith.


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