MONTRÉAL – A molecule developed to combat cocaine addiction represents an interesting therapeutic approach to advanced colorectal cancer, according to a study at the University of Ottawa.
Vanoxerine thus seems able to block the growth of cancer stem cells by modifying the main gene regulatory networks, according to the work of Professor Yannick Benoit and his team.
“Having in our arsenal tools to combat cancer stem cells that are famous, unfortunately, for being resistant to current treatments could mean that once combined with standard drugs, it could greatly increase the chances of survival for patients with advanced stage tumors,” said Professor Benoit, from the Faculty of Medicine at the University of Ottawa.
The effectiveness of vanoxerine in repressing the activity of cancer stem cells has been observed not only in tumors implanted in laboratory animals, but also in the tissues of people with colon cancer.
It is these stem cells, which hide inside tumors, that are probably responsible for the appearance of metastases. Preventing the disease from spreading to other organs would therefore represent an equally obvious and undeniable advantage.
Vanoxerine combats cocaine addiction by interfering with a dopamine transport protein, a molecule that causes feelings of pleasure and reward in the brain. But researchers also found, completely unexpectedly, that it represses an enzyme named G9a in colorectal tumors, which essentially makes the disease more vulnerable to immunotherapy treatments.
“We already knew the enzyme G9a for its involvement in maintaining cancer stem cells in colon tumors,” said Mr. Benoit. My lab was already studying it. But the problem is that molecules that have already been developed to block this enzyme are toxic when given systemically.”
Mr. Benoit and his team used a screening method to analyze some 2000 molecules in search of candidates capable of blocking G9a with minimal collateral damage. The researchers were surprised to see vanoxerine emerge from the lot.
“We were a bit fishing,” admitted Mr. Benoit. It is often said that innovation happens somewhat by chance, and I would say that this is a good example.”
That being said, the surprise was not total since studies from a decade ago already suggested that cocaine use could decrease the expression of the enzyme G9a, he added. So there was “a connection” there, he said, “and it’s interesting to see that cocaine and our candidate molecule have the same target.”
Subsequent work then detected the presence of the dopamine transporter in certain colorectal cancer cells.
Vanoxerine is approved for the treatment of cocaine addiction in only a handful of countries. Canada and the United States are not among them, but the molecule has already been the subject of phase III clinical trials, which testifies to its potential.
Colorectal cancer is the second leading cause of cancer-related death in the world and is considered a “silent killer,” as it usually does not cause symptoms in the early stages. Although the risk increases with age, new statistics show a concerning increase in young adults.
Since the disease is often detected at an advanced stage, treatment options are often limited. Colorectal cancer is also often refractory to conventional immunotherapy treatments. Any new therapeutic approach is therefore welcome, said Mr. Benoit.
The findings of this study were published in the medical journal Nature Cancer.
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2024-02-14 00:33:15
