Friday August 14 2009
A spreading breast cancer cell
“Cancer: the end?” is the dramatic headline in the Daily Mirror, which reports that “cancer could be wiped out after scientists found a drug that kills the deadly stem cells which drive the growth of tumours”. The drug, called salinomycin, was found to slow the growth of breast cancers in mice and to be more effective than the chemotherapy drug paclitaxel for preventing stem cells from forming new tumours. However, as the newspaper says, it may be 10 years before this drug is ready for use in humans.
Researching new ways to identify drugs that could potentially treat cancer is very important. This research has developed a way to screen large numbers of chemicals and identify ones that can selectively target breast cancer stem cells. However, whether this method can be used or adapted to identify chemicals that target stem cells from other types of cancer remains to be seen. Although the results on salinomycin seem promising, the drug will need to undergo further testing of its safety and effectiveness in animals before it can be tested in humans. Even if these various rounds of testing were all to prove successful, this would be a lengthy process.
Where did the story come from?
Piyush Gupta and colleagues from the Massachusetts Institute of Technology and other research centres in the USA conducted this study. The research was funded by the Initiative for Chemical Genetics and the National Cancer Institute in the US. The study was published in the peer-reviewed scientific journal Cell.
What kind of scientific study was this?
This was laboratory and animal research aimed at identifying chemicals that could kill a specific kind of cancer stem cell called epithelial cancer stem cells (CSCs). These cells are thought to drive tumour growth and recurrence, and to be resistant to many cancer treatments such as chemotherapy and radiotherapy. In the past these cells have proved difficult to study because there are only a few of them within each tumour and they are difficult to grow in the laboratory.
The researchers wanted to develop a technique to grow CSCs in the laboratory, allowing them to screen a large number of chemicals and identify any that would specifically target and kill the stem cells. They took breast cancer cells (called HMLER cells) growing in the laboratory and tried to increase the proportion of cells that were CSCs by stopping a gene called CDH1 from functioning.
The researchers found that this technique did increase the number of cells that had the characteristics of CSCs. These characteristics include the ability to form tumour-like clumps of cells when grown in a solution and an increased resistance to the chemotherapy drugs paclitaxel and doxorubicin. They found that they could also use their method to produce CSCs from non-cancerous breast cells (called HMLE cells).
The researchers then took samples of the non-cancerous breast cells and the CSCs developed from these cells and exposed them to around 16,000 chemical compounds, in order to screen for chemicals that were more effective at killing CSCs than normal cells.
A subset of chemicals that were found to selectively target CSCs were then tested on CSCs produced from the HMLER breast cancer cells and the HMLER breast cancer cells themselves. Chemicals that also showed selective targeting of the CSCs in this experiment were studied using further laboratory tests and then finally using tests in mice which had been injected with breast cancer cells .
What were the results of the study?
Among the thousands of chemicals that were tested the researchers identified 32 chemicals that were more effective at killing breast CSCs than at killing non-cancerous breast cells in the laboratory tests. This included three chemotherapy drugs. Eight of these chemicals were given further testing. Only one of the chemicals, salinomycin, was also more effective at killing breast-cancer-cell derived CSCs than the original (mostly non-CSC) breast cancer cells.
Salinomycin was better at killing breast CSCs than the chemotherapy drug paclitaxel, and salinomycin was also able to kill CSCs that were resistant to paclitaxel treatment. Following this researchers treated breast cancer cells with salinomycin in the laboratory, and then injected them into mice: salinomycin pre-treatment reduced the number of mice that developed tumours compared to mice injected breast cancer cells that had been treated with paclitaxel. Injecting salinomycin into mice with breast (mammary) tumours slowed the growth of these tumours.
What interpretations did the researchers draw from these results?
The researchers conclude that they have shown that it is possible to identify chemicals that specifically kill CSCs.
What does the NHS Knowledge Service make of this study?
While research looking into individual drugs to fight cancer is important, the importance of new ways to identify these drugs in the first place should not be underestimated. One key implication of this research is the development of a technique to screen chemicals en masse and identify those that kill breast cancer stem cells. Whether this method can be used or adapted to identify chemicals that target CSCs from other types of cancer remains to be seen.
Although the results for salinomycin seem promising, thusfar it has only been tested on cells grown in the laboratory and initial experiments in mice, and it will need to undergo further testing of its effectiveness and safety in animals before researchers know whether or not it looks promising and safe enough for human tests.