2024-02-13 21:33:15
MONTREAL — A molecule developed to combat cocaine addiction represents an interesting therapeutic avenue in the face of advanced colorectal cancer, suggests a study carried out 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 tools in our chest to fight cancer stem cells which are famous, unfortunately, for resisting current treatments might mean that, once combined with standard drugs, it might greatly increase the chances of survival for patients with advanced tumors,” said Professor Benoit, of the Faculty of Medicine at the University of Ottawa.
The effectiveness of vanoxerine in suppressing the activity of cancer stem cells has been noted 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, which are probably responsible for the appearance of metastases. Preventing the disease from spreading to other organs would therefore represent an advantage that is as obvious as it is undeniable.
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 called G9a in colorectal tumors, which essentially has the effect of making the disease more vulnerable to immunotherapy treatments.
“We already knew the G9a enzyme for its involvement in the maintenance of cancer stem cells in colon tumors,” said Mr. Benoit. My lab was already studying it. But the problem is that the molecules that have already been developed to block this enzyme are toxic when given systemically.”
Mr. Benoit and his team therefore used a screening method to analyze some 2,000 molecules in search of candidates capable of blocking G9a with minimal collateral damage. The researchers were surprised to see vanoxerine emerge from the pack.
“We went fishing a little,” admitted Mr. Benoit. We often say that innovation happens a bit by chance, and I would say that this is a good example.”
That being said, the surprise was not total since studies dating back around ten years already suggested that cocaine consumption might reduce the expression of the G9a enzyme, he added. So there was “a link” there, he said, “and it’s interesting to see that cocaine and our candidate molecule have the same target.”
Subsequent work then made it possible to detect the presence of the dopamine transporter in certain colorectal cancer cells.
Vanoxerine is only approved for the treatment of cocaine addiction in a handful of countries. Canada and the United States are not part of it, but the molecule has already been the subject of phase III clinical trials, which demonstrates its potential.
Colorectal cancer is the second leading cause of cancer-related death worldwide and is considered a “silent killer” because it usually does not cause symptoms in the early stages. Although the risk increases with age, new statistics show an alarming rise among young adults.
Since the disease is often detected at an advanced stage, treatment options are often limited. Colorectal cancer is also frequently refractory to conventional immunotherapy treatments. Any new therapeutic avenue is therefore welcome, said Mr. Benoit.
The findings of this study were published by the medical journal Nature Cancer.
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