Old drug could have new use as cancer stem cell destroyer
Published Thursday, May 24, 2012 6:02PM EDT
An old drug once routinely used as a treatment for schizophrenia appears to have a hidden talent, Canadian researchers have discovered: neutralizing cancer stem cells while leaving healthy cells intact.
The discovery is an important one, since traditional chemotherapy and radiation often fail to eradicate cancer stem cells, which are cells that can lurk in the body, replicating themselves over and over, causing certain kinds of cancer to return.
But a team of scientists at McMaster University has discovered that thioridazine, a medication used as the antipsychotic and to treat Parkinson's disease, can target cancer stem cells and change them into cells that are non-cancerous.
And unlike chemotherapy and radiation, thioridazine appears to have no effect on normal stem cells, which could mean side effects like hair loss.
The team at McMaster's Stem Cell and Cancer Research Institute made their finding while testing hundreds of compounds using an automated robotic stem cell screening system. Thioridazine was one of about a dozen already-known compounds that the robotic team found had good potential as cancer treatments.
Thioridazine is known to work as a psychiatric and Parkinson's medication by targeting receptors in the brain for dopamine, which is a neurotransmitter that plays a variety of roles in the brain.
It turns out that leukemia cells have a dopamine receptor on their surfaces too — making them vulnerable to the drug. The drug doesn't kill these cancerous stem cells, but rather encourages them to become normal again.
The team's research is published in the science journal, Cell.
Mick Bhatia, the principal investigator for the study and scientific director of the Institute, says what makes this drug so exciting is that it has already been approved for use in patients.
"I think it is fascinating because the drug has already been used already -- albeit for another purpose; here it is being repurposed for cancer. The fact that all that workup has been done already allows us to move this into the clinic quickly," he says.
The next step is to test thioridazine in clinical trials on cancer patients. The first study will focus on 30 patients with acute myeloid leukemia, or AML, whose disease has relapsed after chemotherapy.
The team wants to find out if the drug can put their cancer into remission, and prevent it from returning, says co- investigator Terry Sachlos.
"By targeting the rare population of cells that seed, that drive the cancer, what we are hoping with the drug is to eliminate those cells and prevent patients from getting sick again," he says.
While researchers are excited, there are some concerns about side effects. Thioridazine was once widely used as a psychiatric medication, but its use has been curtailed after studies showed it can lead to heart and eye problems in patients taking it long term.
Health Canada took thioridazine off the market in Canada in 2005 after reports it could boost the risk of rare but potentially fatal changes in heart rhythm. Those problems happened only in patients who took the drug daily for more than two years. Bhatia says that for the cancer study, the drug would be used in low doses for about 20 to 30 days, much like standard chemotherapy.
A note of caution – many drugs that show effects in the lab may not work in people, so this is an exciting but very preliminary finding, say doctors.
In the future, thousands of other compounds will be analyzed with the McMaster robotic stem cell screening system in partnership with collaborations that include academic groups as well as industry.
"The goal for all of the partners is the same -- to find unique drugs to change the way we tackle and treat cancer," says Bhattia.
Dr. Anargyros Xenocostas, a cancer specialist from London Health Sciences Centre who was a co-author of the study, says while the results are exciting, there is still a long way to go before it becomes clear whether this drug will prove to be a new therapeutic avenue.
He's anxious to begin testing the drug in patients with AML to see if the medication works as well in humans as it does in cancer cells in a lab.
With a report from CTV medical specialist Avis Favaro and producer Elizabeth St. Philip