• 7/19/2004
  • Calgary, Canada
  • Nature Cell Biology

U of C professor Patrick Lee is working on using the herpes simplex virus to kill cancer cells. A common virus is proving to be a powerful agent in the fight against cancer. Patrick Lee, professor at the University of Calgary oncology department, has discovered how an engineered form of the herpes simplex virus kills cancer cells.

“This is a major conceptual breakthrough in the design of viruses against cancer,” he said. The study of viral therapy — the use of common viruses such as the herpes simplex virus to destroy cancer cells while keeping healthy cells intact — is not new. Cancer researchers have been studying the process for a decade, but before Lee’s discovery, researchers did not understand exactly why the herpes virus is a potent cancer killer. The discovery, suggests Lee, will speed research into viral therapies for cancers.

The article detailing the findings was published in the scientific journal Nature Cell Biology. “Lee’s work provides an important link in our understanding of how viruses can be genetically engineered to attack cancer,” said Dr. Robert L. Martuza, a professor of neurosurgery at Harvard University medical school. Martuza, who is not part of Lee’s research team, is a leading researcher in how the herpes simplex virus acts as a cancer-killing agent. He is conducting human trials on the use of the herpes virus as a cancer therapy. “What Dr. Lee has done is identify a cancer pathway, and there are numerous cancer pathways. This is one building block in the whole scheme of things, but ultimately in the next few years, what we would have are viruses that are specific to cancer pathways A, B or C,” said Martuza. “So, for example, if you had a tumour diagnosed in you, we would identify which pathway is wrong and we would have a virus that would attack that pathway. Dr. Lee has provided a mechanism in providing the specificity of these viruses that we are making for cancer therapy.”

Lee is known for his work with the reovirus, a naturally occurring bug that poses no threat to humans yet can destroy cancer cells with amazing accuracy. He became interested in the herpes virus because he was curious to see whether other viruses work the same way as the reovirus in fighting cancers. “The herpes virus kills cancer cells through the Ras pathway. To understand the Ras pathway, you have to know the difference between a normal cell and a cancer cell,” said Lee. “There is a biochemical process called the Ras pathway in all cells that regulates cell growth. In normal cells, this process is tightly regulated. “In cancer cells, because of mutation, this pathway becomes very active.” Lee compares the cell to a room and the Ras pathway to a light switch in the room. “In normal cells, the Ras pathway is a light switch that is turned on only part of the time, and most of the time it’s switched off, because this pathway regulates cell growth. But in a cancer cell, the Ras pathway is on all of the time. And that is why you get cancer: because the light can’t be turned off and the cancer cells don’t die and keep on growing.”

But Lee discovered the herpes virus “loves the Ras pathway. “That is why when herpes cells go into a normal cell, they say, ‘Hey I can’t do anything because the light is turned off. But when they get into a cancer cell, the light is turned on and they say, ‘I can use that’ and boom they infect the cancer cell. The herpes virus then takes over the cell by making use of its resources to replicate itself, the cell then ruptures releasing virus particles which rapidly infects neighbouring cancer cells, killing them all.”

An individual injected with the modified virus would not become infected with herpes because the virus has been disarmed. In discovering how the herpes simplex virus infects cells, Lee said that it will also help researchers explore new drugs to control herpes infections.