Imagine having access to a cancer-fighting treatment that doesn’t come with the toxic side effects of conventional treatments, like chemotherapy or radiation. Well, thanks to Mick Bhatia and a team of researchers at the McMaster Stem Cell and Cancer Research Institute, we’re on the brink of exactly that.
Bhatia has discovered that the drug known as thioridazine can successfully kill cancer stem cells while leaving the normal, healthy cells relatively unscathed. However, for Bhatia, that’s not even the most intriguing part of the discovery.
“The unusual aspect of our finding is the way this human-ready drug actually kills cancer stem cells by inducing differentiation,” he says. “It changes them into cells that are non-cancerous.”
The research was published in the May 24, 2012 issue of the science journal CELL, and the innovation is the next step in Ontario’s role in the discovery of the link between cancer and stem cells.
It was back in 1997 that researchers at the University of Toronto first discovered cancer stem cells in certain types of leukemia. Today, they’ve been identified in blood, breast, brain, lung, gastrointestinal, prostate, and ovarian cancers.
Bhatia, as the principal investigator for the study and the scientific director of the McMaster Stem Cell and Cancer Research Institute of the Michael G. DeGroote School of Medicine, believes the new finding holds the promise of bringing to life a new strategy and discovery pipeline for the development of anti-cancer drugs in the treatment of various cancers. In fact, the team has identified another dozen drugs that have good potential for a similar response.
To flesh out the promise, McMaster researchers have already pioneered a fully automated robotic system to identify several drugs, including thioridazine, and their effects not only on cancerous stem cells, but on normal ones as well.
“Now we can test thousands of compounds,” Bhatia says. “Eventually, we’ll be able to define a candidate drug that has little effect on normal stem cells but kills the cells that start the tumour.”
Once that’s been established, Bhatia says the next step is to test thioridazine in clinical trials, focusing on patients with acute myeloid leukemia whose symptoms have relapsed after chemotherapy. He wants to determine whether or not, by targeting cancer stem cells, the drug can prevent the cancer from coming back.
The wheels are already in motion. Bhatia’s team at McMaster has found that thioridazine works through the dopamine receptor on the surface of the cancer cells in both leukemia and breast cancer patients. This means that 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 too.
From here, the team plans to investigate the effectiveness of the drug in other cancers, explore several other drugs identified along with thioridazine, and begin to analyze thousands of other compounds using McMaster’s robotic stem cell screening system—the latter, in partnership with academic groups as well as industry.
“The goal for all of the partners is the same,” Bhatia says. “We all want to find unique drugs that will change the way we tackle and treat cancer.”
The research was funded by the Ontario Consortium of Regeneration inducing Therapeutics (OCRiT), which is an arm of Ontario’s Ministry of Economic Development and Innovation, the Canadian Institutes of Health Research, the Canadian Cancer Research Institute, as well as private donors. Bhatia says such a large scale research endeavour would have been impossible without their support and vision.
