May 25, 2012
New Drug Kills Cancer Cells Without Toxic Effects
Connie K. Ho for RedOrbit.com
A group of researchers from McMaster University have found a new drug that can kill cancer stem cells in humans while avoiding the toxic side effects of other traditional cancer treatments.
Over the past 15 years, researchers have thought that stem cells were the cause of many cancers. Canadian researchers first discovered cancer stem cells in particular types of leukemia in 1997. Since then, cancer stem cells have been found in blood, breast, brain, gastrointestinal, lung, ovarian, and prostate cancer.
"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," explained 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, in a prepared statement.
The anti-psychotic drug, thioridazine, showed to have no effect on normal stem cells in the study. In the past, thioridazine had been used to treat schizophrenia. The research, published in a recent edition of the science journal CELL, describes the new method and alludes to possible development of anticancer drugs to treat different cancers. Thioridazine has the ability to make the cancer stem cells differentiate into less threatening stem cell types. The research team also determined other drugs that could possibly elicit the same response as thioridazine.
"You have to find something that's truly selective for cancer stem cells," continued Bhatia in the statement. "We've been working for some time and it's hard to find that exact formula."
In the project, the group of researchers examined a dozen different compounds, including thioridazine, with a fully automated robotic system. The researchers were screening hundreds of compounds to find those cells that would selectively inhibit human cancer stem cells. With thioridazine, leukemia cells were eliminated but without affecting normal blood stem cells. The researchers were better able to understand the specificity after comparing proteins in leukemia to normal blood cells. While leukemia cells express a dopamine receptor on their surfaces, normal stem cells do not.
"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," commented Bhatia in the statement.
In continuing the project, the researchers want to look at the effects of thioridazine in clinical trials. They hope to better understand how patients with a relapse of acute myeloid leukemia after chemotherapy fare with the drug. In particular, Bhatia wants to investigate if thioridazine can put cancer in remission and prevent the cancer from coming back. He hopes to do this by targeting the cancer stem cells, which are known to be the root of the disease. Researchers at McMaster University have already started on this initiative, having successfully designed the format of the clinical trials.
Various groups like the Canadian Institute of Health Research (CIHR), the Canadian Cancer Society Research Institute (CCSRI), the Ontario Ministry of Economic Development and Innovation (MEDI), and the Ontario Consortium of Regenerating inducing Therapeutics (OCRiT) support the study with funding grants.
"The goal for all of the partners is the same — to find unique drugs to change the way we tackle and treat cancer“¦ 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," concluded Bhatia. "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."