Everyone has heard about stem cells derived from normal tissues and the promise they hold in curing serious illnesses such as diabetes, Parkinson’s disease, and spinal cord paralysis. But did you know that cancerous tumors also contain stem cells and that specifically targeting them may lead to a far more effective treatment?
We now know that over 99% of the cells that make up a cancer are well along in their lifespan, so much so that many can no longer divide, while others actually die off. The remaining 1% (or less) are primitive stem cells that act as malignant “seeds” that can spring to life, even after apparently successful treatment, and spread the disease throughout the body.
In fact, oncologists now suspect that currently-available treatments often fail to eradicate cancer because they only shrink the population of older cells, leaving the stem cells behind.
Why does this happen? Because, unlike the older cells, cancer stem cells are “bullet-proof” in their resistance to chemotherapy drugs and radiation. Their numbers actually increase dramatically as the majority of susceptible, non-stem cancer cells are killed off by treatment. The result: tumors that are now impervious to attack.
Until recently, identifying chemicals that might specifically take on cancer stem cells has been seriously hampered by an inability to isolate enough of them to test in the laboratory. However, new research suggests that this is about to change.
In a paper just published in the prestigious journal, Cell, scientists at the Massachusetts Institute of Technology and Harvard University have come up with a way to convert “ordinary” normal and malignant cells of human origin into those that look and behave like stem cells.
They achieved this remarkable feat by blocking a single gene, CDH1, that produces E-cadherin, a cell protein that normally makes cancer cells stick tightly together. Without E-cadherin, breast cancer cells showed an increased ability to metastasize (spread), and took on stem-like properties, including resistance to paclitaxel (Taxol), a normally powerful chemotherapy drug.
Then, with the ability to make millions of stem cells to test, the researchers used a “high-throughput” method to screen 16,000 chemicals for their stem cell-killing ability. They identified 32 active compounds. Salinomycin, an antibiotic widely employed in the poultry industry, was the most potent of these and selected for further testing.
In subsequent experiments, salinomycin proved to be over 100 times more powerful than paclitaxel to reduce the number of stem cells among a population of breast cancer cells. Salinomycin also blocked a series of other genes specifically associated with stem cells. And, consistent with its anti-stem cell effects, it significantly reduced the ability of injected breast cancer cells to take hold, grow and metastasize, in mice.
The exact mechanism by which salinomycin “pierces the bullet-proof vest” of cancer stem cells remains to be determined. Like many antibiotics, the drug is an “ionophore”, and can significantly alter levels of cell potassium. Perhaps the stem cells are much more sensitive than other cancer cells to any change in the normal balance between potassium and other electrically-charged ions, such as sodium and calcium.
Despite these exciting findings, scientists are quick to point out that, because salinomycin has never been approved for human use, its safety and effectiveness is unknown. In fact, based on one reported case of accidental salinomycin poisoning in a poultry worker, the drug could prove far too toxic at doses required to treat humans with cancer.
At the moment, what is important is being able to consistently produce large numbers of cancer stem cells in the laboratory so that many other agents can be tested against them, and so that researchers can gain a better understanding of their unique biology.
What’s down the road? Hopefully, by combining conventional chemotherapy and radiation with effective new drugs that target cancer stem cells, we will achieve a whole new level of success in the war against cancer.