Thioridazine kills cancer stem cells in human while avoiding toxic side-effects of conventional cancer treatments

May 24, 2012

A team of scientists at McMaster University has discovered a drug, thioridazine, successfully kills cancer stem cells in the human while avoiding the toxic side-effects of conventional cancer treatments.

"The unusual aspect of our finding is the way this human-ready drug actually kills cancer stem cells; by changing them into cells that are non-cancerous," said Mick Bhatia, the principal investigator for the study and scientific director of McMaster's Stem Cell and Cancer Research Institute in the Michael G. DeGroote School of Medicine.

Unlike chemotherapy and radiation, thioridazine appears to have no effect on normal stem cells.

The research, published today in the science journal Cell, holds the promise of a new strategy and discovery pipeline for the development of in the treatment of various cancers. The research team has identified another dozen drugs that have good potential for the same response.

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Interview with Mick Bhatia

For 15 years, some researchers have believed stem cells are the source of many cancers. In 1997, Canadian researchers first identified cancer stem cells in certain types of leukemia. Cancer stem cells have since been identified in blood, breast, brain, lung, gastrointestinal, prostate and .

To test more than a dozen different compounds, McMaster researchers pioneered a fully automated robotic system to identify several drugs, including thioridazine.

"Now we can test thousands of compounds, eventually defining a candidate drug that has little effect on normal stem cells but kills the cells that start the tumor," said Bhatia.

The next step is to test thioridazine in clinical trials, focusing on patients with whose disease has relapsed after chemotherapy. Bhatia wants to find out if the drug can put their cancer into remission, and by targeting the root of the cancer (cancer ) prevent the cancer from coming back. Researchers at McMaster have already designed how these trials would be done.

Bhatia's team found thioridazine works through the dopamine receptor on the surface of the cancer cells in both leukemia and breast cancer patients. This means it may be possible to use it as a biomarker that would allow early detection and treatment of breast cancer and early signs of leukemia progression, he said.

The research team's next step is to investigate the effectiveness of the drug in other types of cancer. In addition, the team will explore several drugs identified along with thioridazine. In the future, thousands of other compounds will be analyzed with 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," he said.

The research was supported by grants from the Canadian Institute of Health Research (CIHR), the Canadian Society Research Institute (CCSRI) and the Ontario Ministry of Economic Development and Innovation (MEDI)'s Ontario Consortium of Regenerating inducing Therapeutics (OCRiT).

"This large scale research endeavor would have been impossible without the active support and vision of the Canadian and Ontario governments along with private donors," said Bhatia.

Explore further: Therapy targets leukemia stem cells

More information: Sachlos et al.: “Identification of Drugs Including a Dopamine Receptor Antagonist that Selectively Target Cancer Stem Cells.” Cell.

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Yevgen
not rated yet May 24, 2012
This is amazing stuff, considering that thioridazine is an
antipsychotic drug that is intended for continuous use, so its
side effect are definitely mild compared to traditional chemo. Of case we have to see what effective dosage will turn out to be, if any. It might be much higher then for original use, so side effects will also increase.
C Alexander Brown
not rated yet May 25, 2012
This is a very encouraging and heartening discovery. It will be very interesting to see if thioridazine is effective against Multiple Myeloma.
DoubleD
not rated yet May 25, 2012
This is amazing stuff, considering that thioridazine is an
antipsychotic drug that is intended for continuous use, so its
side effect are definitely mild compared to traditional chemo. Of case we have to see what effective dosage will turn out to be, if any. It might be much higher then for original use, so side effects will also increase.


For all patients:

Thioridazine can cause a serious type of irregular heartbeat that may cause sudden death. There are other medications that can be used to treat your condition that are less likely to cause this life-threatening side effect. Therefore, you should not take thioridazine unless you have already been treated with at least 2 other medications for your condition and these medications did not work well or caused side effects that you could not tolerate.

Hopefully the dosage will be similar or lower!
Paradox
not rated yet May 28, 2012
"Thioridazine can cause a serious type of irregular heartbeat that may cause sudden death."

Really? How many people have you seen die from cancer. I have seen several. Current methods do not work, they only give a temporary reprieve at best. Meanwhile, your immune system will be destroyed so your body's ability to combat anything is gone., Your bones will be degraded, hair loss, diarrhea, vomiting, and a myriad of other health problems from the so called "cure". It is a farce to make drug companies rich. ANY alternative method is better than the current methods, I can tell you.
Irregular heartbeat? I would rather go with that, instead of dying from the Chemo like some of my relatives.
KatLom
not rated yet May 29, 2012
Wonderful! Another promising cancer treatment that will hit the headlines for a week or so and then be buried, never to be seen again, by the pharmaceutical companies.

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