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Virus most effective weapon against cancer

by Archives September 23, 2008

Researchers at McGill and Ottawa University have announced a breakthrough in the use of viruses in cancer therapy. The discovery may lead to a significant increase in the number of cancer cells that can be eliminated during treatment.
The findings show a family of molecular compounds that, when used in combination with a virus harmless to humans, greatly increases the virus’ ability to identify and eliminate cancer cells. This discovery may offer a way to target cancer cells that are resistant to conventional surgeries and radiation therapy. Dr. John Hiscott, head of the McGill research team, was surprised at how effective the combination of the virus and molecules, called histone deacelytase inhibitors (HDIs), was in targeting and destroying cancer cells while leaving normal cells unharmed.
“Cancer cells, in the course of developing and growing rapidly, as all cancer cells do, actually lose the capacity to fight off viral infections,” he said. “Now the virus can infect and replicate in those cells without any limiting factors, such as exist in normal cells that limit virus multiplication through the immune system.”
The HDI strain’s effects were observed in animal tests conducted in Ottawa and in cell cultures and human tissue samples from breast, prostate and colon cancer patients at the Lady Davis Research Institute in Montreal.
“The therapeutic index measures the amount of cancerous cells killed versus the number of normal cells,” said Hiscott. “Whereas in conventional radiation therapy the index is around 10 cancerous cells for every one normal cell, the ratio in virotherapy is around 1,000 to 10,000 cancerous cells destroyed for every normal cell.”
The experiments also showed that continuous HDI administration is needed to maintain a high level of virus replication within the cancer tumour. Dr. Nanh Nguyen, a senior researcher in the Hiscott lab, noted that this allows physicians to get a clearer image of the infection by observing the virus’ progress through the cancerous cells. In addition, the control over replication that HDIs provide could possibly serve as a safety precaution when dealing with types of cancer in which an unwanted response to the treatment, such as a swelling of a tumour in the brain when a virus attacks the cancer cells, can be prevented by lessening the dosage.

“We really showed that the HDI inhibitor can be used as a chemical switch, so it’s possible we can increase or decrease the virus’ replication in accordance with the health of the patient,” she said. The virus to which the compound is combined is a non-human pathogen, originally derived from insects. Its molecular biology as well as its replication behaviour have been studied by virologists for several decades and are well understood. The familiarity with this virus helps minimize potential risks to humans, and the discovery of its replication levels as they increase when combined with the HDI strain could be the key to developing new therapies for breast, prostate, colon and other primary cancers that are resistant to regular virotherapy.
This breakthrough heralds new challenges for the research teams at McGill and Ottawa, beginning with the task of finding out exactly why this particular strain is so effective.
“The next steps are twofold, one is to further understand the basic mechanism of what’s going on here, why the HDI’s are so powerful in stimulating virotherapy,” said Hiscott. “The other is understanding the different types of combinations that might be most effective in dealing with different types of cancers.”
There also remain a number of review boards to go through before human trials can begin. However, the presence of certain virus treatments already in the human trial stages, as well as the American Federal Drug Administration-approved use of HDI inhibitors in the treatment of leukemia, could push this treatment into human trials sooner rather than later.

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