TORONTO — Canadian scientists believe they have found the “Achilles heel” of colon cancer stem cells, which appear to be responsible for the recurrence of the disease in many patients who have gone into remission after treatment.
Researchers at Toronto’s University Health Network have used an experimental drug to disable a gene that regulates these stem cells, which are thought to initiate the development of colon cancer.
That gene — known as BMI-1 — has been implicated in maintaining stem cells in other cancers, and is the key regulator of colon cancer stem cells that propels their self renewal and proliferation.
Stem cells are the blueprints of the body, which give rise to different types of cells that make up tissues, from red and while blood cells to neurons in the brain and insulin producing cells in the pancreas.
Cancer stem cells, including those identified in the brain, breast and colon, give rise to tissue-specific cancer cells that grow out of control and form tumours.
In Sunday’s issue of Nature Medicine, the Toronto researchers describe experiments in which they disarmed the BMI-1 gene, thereby stopping colon cancer stem cells from generating malignant cells.
The team first used a variety of genetic methods to silence the gene in colon cancer cells taken from patients, which were transplanted into laboratory mice specially bred not to reject human tissue.
“And it just wiped out the ability of these cells to make new tumours,” said principal researcher John Dick, a senior scientist at Princess Margaret Cancer Centre and director of the cancer stem cell program at the Ontario Institute for Cancer Research. “We showed that if you turn this thing down, the colon cancer stem cells, they’re not stem cells anymore. They lose their function.”
The team then took human colon cancer cells — which would have included cancer stem cells in the mix — and exposed them to a drug being developed as an inhibitor of the BMI-1 gene and the protein it expresses.
These treated cells were transplanted into mice with the goal of seeing whether the drug would disable cancer stem cells and stop them from spurring the growth of new tumours. “And it did,” said Dick. “It worked remarkably well.” The team tested the drug by administering it to mice. After transplanting human colon cancer cells into mice, they waited for tumours to develop and began injecting the rodents with the drug.
“We showed there was a massive reduction in tumour growth when we treated the mice with the drug,” said Dick.
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