The finding, published in the journal Cell Press, was made after screening hundreds of compounds in search of those that would selectively inhibit human cancer stem cells. The discovery may be evaluated in a clinical trial in the very near future.
Leading author, Mickie Bhatia, from McMaster University declared:
"You have to find something that's truly selective for cancer stem cells. We've been working for some time and it's hard to find that exact formula."
Over the last three decades, cancer survival in patients has remained largely unchanged. Many scientists believe that the likelihood of finding a cure will be greater by addressing the rare and chemotherapy-resistant cancer stem cells.
In contrast to normal stem cells, cancer stem cells are resistant to changing into stable, non-dividing cells types. The researchers used this difference to simultaneously screen compounds against human cancer stem cells to normal human stem cells.
After testing hundreds of compounds, they discovered almost 20 potential cancer stem cell specific drugs, with the antipsychotic drug thioridazine being the most promising of all. Thioridazine is a schizophrenia drug that targets the brain's dopamine receptors. Although the drug does not seem to kill cancer stem cells, it encourages them to differentiate and therefore exhausts the number of self-renewing cells.
By comparing the proteins in leukemia to normal blood cells the researchers established that thioridazine kills leukemia stem cells without affecting normal blood stem cells. Unlike normal blood stem cells, the leukemia stem cells express a dopamine receptor on their surfaces, which also appear on some breast cancer stem cells.
Bhatia said: "This gives us some explanation." It also indicates that dopamine receptors could be biomarkers for rare, tumor-initiating cells.
After their discovery, Bathia's team is currently planning a clinical trial of thioridazine in combination with standard anti-cancer drugs for adult acute myeloid leukemia. Bathia concludes: "We're excited about bringing this drug to patients. We also hope our platform can now be a pipeline for other cancer stem cells drugs."
Written By Petra Rattue