US researchers have discovered a compound that can kill breast cancer stem cells, a kind of master cancer cell that resists conventional treatment and may explain why many cancers grow back, they reported Thursday. The discovery came using a new method of screening for drugs that specifically target and kill cancer stem cells, and it could be used to find drugs targeting other cancer stem cells as well, they said. Many teams have been looking for ways to destroy these master cancer cells in hopes of making cancer easier to cure. “There is a lot of evidence to suggest now that these cells are responsible for many of the recurrences that are observed after treatment has stopped,” Piyush Gupta of the Massachusetts Institute of Technology and the Broad Institute, whose study appears in the journal Cell, said in a telephone interview Thursday. The problem is that cancer stem cells are rare and difficult to study in the lab because they quickly change into other types of cells. And they are hard to kill. “It wasn't clear it would be possible to find compounds that selectively kill cancer stem cells,” Gupta said in a statement. “That's what we did.” To study the cells, Gupta's team first devised a method for stabilizing cancer stem cells in the lab and getting them to multiply. They then tested them against 16,000 natural and commercial chemical compounds to see which ones were able to kill the cancer stem cells specifically. That turned up 32 contenders. They narrowed down this list to a handful of chemicals, and tested these in the lab and in mice. A chemical called salinomycin hit the target. It was 100 times more potent at killing breast cancer stem cells than Bristol-Myers Squibb Co's cancer drug Taxol, or paclitaxel. Cancer stem cells treated with salinomycin were far less able to start breast cancers when injected into mice than cancer stem cells treated by paclitaxel. And the treatment also appeared to slow the growth of tumors in the mice. Gupta said it is not clear if salinomycin will emerge as the best drug compound for killing breast cancer stem cells - or that it will be safe to use in people with cancer. But the study offers a new roadmap for drug companies to isolate and test compounds capable of killing the cells. “We now have an approach that can be used very systematically to find such compounds,” he said. Self-renewing Researchers are still trying to understand the role cancer stem cells play in promoting different types of cancer, but many teams think they may explain why so many cancers come back even after treatment with powerful chemotherapy and radiation. “The theory is these cells are self-renewing, which means they can make identical copies of themselves,” Robert Weinberg of MIT, who worked on the study, said in a telephone interview. “They have the power to generate a new tumor, and they are resistant to existing anti-cancer therapeutics. That suggests the need to develop therapies for cancer stem cells,” he said. Weinberg said it will take several years before therapies targeting cancer stem cells can be used in people. But the finding does hold promise for a new way of looking for cancer treatments. “Ideally, if one hit the cancer stem cell, sooner or later the bulk of the cells of the tumor, which lack a self-renewal capability, would gradually poop out and the tumor would eventually die just by attrition,” Weinberg said.
