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Toronto (Sept. 23, 2006) - Scientists at University Health Network have found a drug that targets the stem cells responsible for acute myeloid leukemia and eradicates those cells in mice transplanted with the human disease.
The scientists discovered that for leukemia stem cells to survive, they must traffic to and adhere to specific places in the bone marrow called niches. The new drug is a monoclonal antibody that interferes with a protein called CD44 on the surface of the leukemia stem cells. When the protein is blocked, the cells are unable to traffic to the niches and as a result, they die. When given to mice transplanted with human acute myeloid leukemia, the drug destroyed the leukemia stem cells and cured many of the animals. The drug is not presently available for use in humans.
"This discovery is exciting because we've devised a new drug that targets a specific property and protein of cancer stem cells without harming normal stem cells," says Dr. John Dick, the study's principal investigator and senior scientist at Ontario Cancer Institute, the research institute of Princess Margaret Hospital (University Health Network). Dr. Dick is also senior scientist at Toronto General Research Institute (University Health Network), Canada Research Chair in Stem Cell Biology, and professor of molecular and medical genetics at the University of Toronto.
"This new understanding opens up all of the molecules involved in these stem cell processes as potential targets for new drugs," says Dr. Dick. "The insight could also be applicable to the stem cells involved in other types of cancers."
The paper will be published on-line September 24 in the international science journal Nature Medicine.
Traditional chemotherapy kills cells that grow quickly and in doing so, it reduces the bulk of tumour cells. But researchers are finding that not every tumour cell grows uniformly. In fact, tumours are sustained by rare cancer stem cells, which grow slowly and are therefore able to survive chemotherapy. For this reason, cancer can recur after treatment.
"The problem is the cancer stem cells can be swimming in a sea of chemotherapy agents and they won't be touched by it," says Dr. Dick. "To cure cancer, we have to get rid of the cancer stem cells by targeting their unique properties."
The Canadian Cancer Society estimates that 4100 Canadians will be diagnosed with leukemia, and that 2200 Canadians will die of the disease in 2006. Leukemia is cancer of the blood system. Blood is composed of plasma liquid, white blood cells to fight infection, red blood cells to transport oxygen, and platelets to control bleeding.
These cells are derived from stem cells, which are produced in the bone marrow and other organs. Stem cells are rare and slow growing cells that self-perpetuate and create other blood cells.
Dr. Dick's team collaborated with Dr. Florence Smadja-Joffee in France, whose lab produced the antibody and is now developing the drug for further study in humans. The work was carried out by Liqing Jin and Kristin Hope in Dr. Dick's lab.
The research was supported by a Canadian Institutes of Health Research studentship and fellowship, grants from the Leukemia and Lymphoma Society, Fondation de France, Association pour la Recherce sur le Cancer and grants from the National Cancer Institute of Canada with funds from the Canadian Cancer Society and the Terry Fox Foundation, Canadian Institutes of Health Research, Ontario Cancer Research Network (now a program of the Ontario Institute for Cancer Research), Genome Canada through the Ontario Genomics Institute, and a Canada Research Chair.
University Health Network is a major landmark in Canada's healthcare system, and a teaching hospital of the University of Toronto. Building on the strengths and reputation of each of our three hospitals and affiliated research institutes, Toronto General Hospital, Toronto Western Hospital and Princess Margaret Hospital, UHN brings together the talent and resources needed to achieve global impact and provide exemplary patient care, research and education.
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