Drug could attack ‘the root’ of cancer cells: study
The findings, published in the journal Cell, have yet to be proven in humans and clinical trials may reveal thioridazine is not effective at treating cancer.
But the initial discovery is creating excitement among cancer experts who have been looking for ways to target cancer stem cells.
Until the 1990s, scientists didn’t know such a thing as cancer stem cells existed. They assumed cancer arose from ordinary cells that have somehow mutated.
But some scientists turned their attention to stem cells – which have the ability to become any tissue type and multiply infinitely. They postulated that abnormal stem cells are the real culprits behind the growth of many tumours.
Researchers, including cancer stem cell pioneer and Toronto scientist John Dick, identified their presence in leukemia, breast cancer, brain cancer, lung cancer and other types of cancers.
Those findings suggested that cancer stem cells are a subset of regular cancer cells that act as the “starter” agents that can cause tumours to grow and cancerous cells to propagate. Scientists believe they help explain why some patients don’t respond to chemotherapy or radiation; those treatments kill cancer cells, but don’t get to the source of the problem.
Mick Bhatia, lead author of the new study and scientific director of the Stem Cell and Cancer Research Institute at McMaster University in Hamilton, Ont., likened it to cutting dandelions.
“Unless you eliminate the root, it’s just going to come back,” he said.
Dr. Bhatia and his colleagues decided to look for treatments that could target cancer stem cells. They developed a system to test dozens of drugs on cancer stem cells and normal, healthy cells.
It was an extremely challenging task because it required the research team to figure out a way to properly isolate cancer stem cells and healthy stem cells and have them grow outside the body. They found that thioridazine worked at killing the cancer stem cells in leukemia and some types of breast cancer, but left the healthy cells unharmed. The researchers then took cancerous tissue from humans and transplanted it into mice. Once again, thioridazine was effective at targeting the cancer stem cells.
The reason the drug seems to work is that it affects the dopamine receptor in cancer stem cells. Most cells don’t have a dopamine receptor, and Dr. Bhatia said it was surprising to find it in cancer stem cells. It’s possible that cancer stem cells evolved to develop a dopamine receptor pathway, allowing them to propagate without the body being able to stop them.
Now, the next step is to test the drug in human clinical trials to determine how well it works. Researchers hope to test the drug on cancer patients who have not responded to traditional treatments such as standard chemotherapy. If it turns out to work, thioridazine might be used in a wider group of cancer patients.
“If they do respond and we can increase quality of life and potentially even get rid of the cancer, I think it’s the best thing anyone can hope for,” Dr. Bhatia said.
The research team will also continue to test more compounds – Dr. Bhatia hopes to look at thousands – to find more that are effective at fighting cancer stem cells. He said the research team has already identified about a dozen other compounds that could also attack cancer stem cells and leave healthy cells unharmed.
Health Canada ordered thioridazine off the market in Canada in 2005 following reports it could increase the risk of rare, but potentially fatal, changes in heart rhythm.
Dr. Bhatia noted that heart problems typically occur in patients taking thioridazine for a prolonged period; cancer patients would be on it for only a matter of days or weeks. But it’s important to study how the drug works in cancer patients, he said, in order to determine what side effects may occur.