Targeting stem cells

Cancer researcher Patrick Lee (centre) with members of the research team, co-principal investigator Carman Giacomantonio (left) and Paola Marcato, post-doctoral fellow. Missing from the photo is Cheryl Dean, research associate.

Dalhousie Medical School cancer researcher Dr. Patrick Lee has proven that a common virus can infect and kill breast cancer stem cells. This breakthrough finding is published in the current issue of Molecular Therapy, the prestigious journal of the American Society of Gene Therapy.

“We suspected that reovirus might be effective against cancer stem cells, because we have shown time and again how well it destroys regular cancer cells,” said Dr. Lee, Cameron Chair in Basic Science Research at Dalhousie Medical School and the first in the world to discover that a benign and naturally occurring virus could selectively infect and kill cancer cells without harming healthy cells.

It is only within the past few years that the scientific community has understood the full significance of cancer stem cells and the urgent need to find a means of eliminating them.

“Cancer stem cells are essentially mother cells,” explains Dr. Lee. “They continuously produce new cancer cells, aggressively forming tumours even when there are only a few of them.”

Cancer stem cells are difficult to kill as they respond poorly to chemotherapy and radiation. As Dr. Lee notes, “You can kill all the regular cancer cells in a tumour, but as long as there are cancer stem cells present, disease will recur.”

Unlike most cancer studies, which use cancer cell lines developed for laboratory use, this study used fresh breast cancer tissue. This cancer tissue was removed from a patient of Dr. Carman Giacomantonio, an assistant professor of surgery and surgical oncologist at Capital Health. Also the clinical leader of Cancer Care Nova Scotia's surgical oncology network, Dr. Giacomantonio is working with Dr. Lee on the reovirus research, along with research assistant Cheryl Dean and post-doctoral fellow Dr. Paola Marcato, who is funded by the Alberta Heritage Foundation.

“This finding promises to be the basis for a major new approach to dealing with many different types of cancer,” says Dr. Gerry Johnston, Dalhousie Medical School’s associate dean of research. “Clearly, the more we understand about the molecular basis for cancer the better equipped we are to deal with cancer in a very directed fashion – a way that spares healthy tissue and eradicates only the disease.”

“We are incredibly proud to have provided funding for Dr. Lee’s research,” said Nancy Margeson, CEO, Canadian Breast Cancer Foundation – Atlantic Region. “For an organization dedicated to a future without breast cancer, research is the most significant part of our work. To have a breakthrough of this magnitude, substantiates our faith that one day our vision will come true. The thousands of people who have put their belief in the work of CBCF should take pride in this achievement.”

In addition to its ability to kill cancer cells and cancer stem cells, reovirus stimulates the anti-cancer immune system. Since virus therapy also invokes an anti-virus response, Dr. Lee and post-doctoral fellow Dr. Shashi Gujar are working on a way to harness the immune system so it attacks cancer cells while allowing the virus to freely infect and destroy cancerous cells. “Refining this two-pronged approach to killing cancer is our next step,” says Dr. Lee. “We are taking advantage of the natural characteristics of reovirus and the immune system itself to create a powerful virus-based anti-cancer therapy.”

Dr. Patrick Lee.

Dr. Lee’s discovery that reovirus effectively targets breast cancer stem cells has captured the attention of LeadDiscovery, a UK-based organization dedicated to promoting drug discovery and development. LeadDiscovery has identified the finding to be of particular interest to the drug development sector and will feature it in its next update to the global scientific community and pharmaceutical industry.

Dr. Lee is a founding member of the Beatrice Hunter Cancer Research Institute, established on April 2, 2009 to foster a coordinated cancer research effort in Atlantic Canada. The institute was named in honour of the late Beatrice Hunter, whose $12.5 million gift to the Dalhousie Medical Research Foundation transformed cancer research in the region. Among its many benefits, this gift funded the Cameron Chair in Basic Cancer Research. Dalhousie Medical School recruited Dr. Lee to Halifax from Calgary to fill this leadership position in 2003.

Calgary-based Oncolytics Biotech Inc. is testing reovirus in clinical trials to prove the treatments are safe and effective.