Researchers discover drug destroys human cancer stem cells but not healthy ones

A team of scientists at McMaster has discovered that the drug thioridazine successfully  kills cancer stem cells in humans 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 anti-cancer drugs in the  treatment of various cancers. The research team has identified another dozen drugs  that have good potential for the same response.

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 ovarian cancer.

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 acute  myeloid leukemia 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 stem cells – prevent the cancer from coming back. Researchers at  McMaster have already designed these trials.

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.

The team will also explore several drugs identified along with thioridazine. In the future,  thousands of other compounds will be analyzed with the McMaster robotic stem cell  screening system in partnership with collaborators 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,  the Canadian Cancer Society Research Institute and the Ontario Ministry of Economic  Development and Innovation’s Ontario Consortium of Regenerating inducing  Therapeutics.

“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.