A well known medicine for treatment of schizophrenia can be a cancer killer, too. In laboratory studies, the drug eliminated a precursor of leukemia cells without harming normal cells. That means it could give doctors a long way out to eliminate any trace of leukemia patients so that the cancer may never return.
While surgery, chemotherapy and radiation can get rid of tumor cells or leukemia, the cancer often returns months or years later. One culprit may be called cancer stem cells, which give rise to cancer cells. These stem cells are resistant to chemotherapy and radiotherapy, and persist in the body. Some researchers believe that combining conventional cancer drugs with a drug that targets cancer stem cells may be the best way to defeat some cancers. But because these cancer stem cells are rare and difficult to grow in the laboratory, some of these drugs have been identified and none are in clinical use.
Now a Canadian team has found a new way to test drugs that target cancer stem cells. They used human pluripotent stem cells, which are made from cells of embryos or reprogrammed adult cells that have the ability to develop into different types of tissue. There are a few years, stem from the team of Mickie Bhatia cell researchers at McMaster University in Hamilton, Canada, stumbled across multiple lines of pluripotent stem cells that share some characteristics of cancer stem cells: The cells continue to divide and will not develop or differentiate, and more specialized cells.
In her new work, the Bhatia Group tested whether various chemical compounds could coax the cells to differentiate, or mature, in normal cells so that they stop dividing abnormally and die a natural death . The researchers hope that this could be a less toxic way to get rid of cancer stem cells by directly killing cells.
After screening hundreds of compounds, including approved drugs, researchers have found a few that did what they wanted: The chemicals caused cancer stem cells like to differentiate without damaging normal, healthy stem cells needed by the body. One of the most potent compounds was thioridazine, an antipsychotic medication used to treat schizophrenia. The drug also blocked the growth of acute myeloid leukemia (AML) stem cells taken from patients. And he overthrew the number of AML stem cells in mice injected with these cells that have developed leukemia, but spared normal blood stem cells.
When combined with thioridazine, the standard drug used to treat AML was 55 times more powerful in killing AML cells in a laboratory dish he was alone, Bhatia and colleagues report today ' hui in cell . The team is now planning a clinical trial to test the drug combination in 15 AML patients who no longer respond to standard drugs alone. "Our feeling is, as it is approved and this synergistic effect, we want to go directly into the patients," says Bhatia.
The study also revealed a curious finding. Thioridazine, which blocks receptors for the neurotransmitter known as dopamine, also seems to work on leukemia stem cells by blocking these receptors. Bhatia said that so far, no one noticed that cancer stem cells have receptors for dopamine, which normally associated with neuronal signaling and found mainly in the brain. But his group also found them in breast cancer stem cells. It suggests a test that measures the amount of dopamine receptors in samples of blood or tissue can detect cancer or to predict a patient's prognosis.
cancer biologist Piyush Gupta of the Whitehead Institute in Cambridge, Massachusetts, who used a different cellular system to find drugs that target cells cancer stem, he says he would not necessarily expect the pluripotent stem cell system to mimic cancer. But "the relevance is shown convincingly by the authors in the context of a leukemia cancer model."
He and others say they are happy to see a new technique to identify drugs that act against cancer stem cells. But the Hudson Thomas cancer researcher at the Ontario Institute for cancer research in Canada says he would like to know more about the mechanism by which dopamine receptors are cell a cancer stem cell.
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