Researchers report that an antipsychotic drug sometimes used to treat schizophrenia appears to influence cancer stem cells to differentiate into less threatening cell types.
Investigators believe the discovery will be followed with a clinical trial. The findings are reported in the journal Cell.
In the study, scientists analyzed hundreds of compounds in search of those that would selectively inhibit human cancer stem cells.”You have to find something that’s truly selective for cancer stem cells,” said Mickie Bhatia, lPh.D., lead author of the study from McMaster University. “We’ve been working for some time and it’s hard to find that exact formula.”
The research represents a new approach for cancer intervention, a necessary approach as the survival of cancer patients is largely unchanged from 30 years ago.
The new approach for cancer targets rare and chemotherapy-resistant cancer stem cells. Unlike normal stem cells, cancer stem cells resist differentiating into stable, non-dividing cell types.
Bhatia’s team exploited this difference to simultaneously screen compounds for their activity against human cancer stem cells versus normal human stem cells.
By testing hundreds of compounds, they identified nearly 20 potential cancer stem cell specific drugs.
The one that appeared most promising is an antipsychotic drug, thioridazine, which combats the symptoms of schizophrenia by targeting dopamine receptors in the brain. But concerns about side effects of the drug, brand name Mellaril, have meant that far fewer people with schizophrenia are prescribed the drug than newer antipsychotic medications.
Researchers say thioridazine doesn’t appear to kill cancer stem cells, but rather encourages them to differentiate, thus exhausting the pool of self-renewing cells.
Investigators discovered thioridazine kills leukemia stem cells without affecting normal blood stem cells by comparing the proteins in leukemia versus normal blood cells.
Furthermore, leukemia cells, but not normal blood stem cells, express a dopamine receptor on their surfaces. This finding is supported by the discovery of dopamine receptors on some breast cancer stem cells.
“This gives us some explanation,” Bhatia said. It also suggests that dopamine receptors might serve as a biomarker for rare, tumor-initiating cells.
In light of the findings, Bhatia’s team is already planning for a clinical trial of the FDA-approved thioridazine in combination with standard anti-cancer drugs for adult acute myeloid leukemia.
“We’re excited about bringing this drug to patients,” Bhatia said. “We also hope our platform can now be a pipeline for other cancer stem cells drugs.”
Source: Cell Press