A screen for cancer killers

Method identifies drugs that target the cells behind cancer growth.

A new approach for identifying drugs that specifically attack cancer stem cells, the cellular culprits that are thought to start and maintain tumour growth, could change the way that drug companies and scientists search for therapies in the war against cancer.

"We now have a systematic method that had not been previously known that allows us to find agents that target cancer stem cells," says Piyush Gupta of the Massachusetts Institute of Technology and the Broad Institute in Cambridge, Massachusetts, and first author of the study, published online today in Cell. Applying the technique, Gupta and his colleagues discovered one of the first compounds that can selectively destroy cancer stem cells. The drug, an antibiotic commonly fed to pigs and chickens, reduces the proportion of breast cancer stem cells by more than 100-fold compared with a drug widely used in chemotherapy for breast cancer.

Although most cancer therapies wipe out the vast majority of tumour cells, they have not been able to eliminate the cause of the disease — the cancer stem cells — so the cancer often comes roaring back with a vengeance. Researchers have looked for drugs that preferentially target cancer stem cells, but these repeat-offender cells are so rare that screening for potential compounds has been nearly impossible. The study team, led by Robert Weinberg and Eric Lander, also from the Massachusetts Institute of Technology, exploited a trick, boosting the number of cancer-stem-cell-like cells to find a molecular missile that homes in on the real target.

By silencing a specific gene in breast cancer cells, the researchers coaxed them to convert from epithelial cells, which make up most of the human body, into mesenchymal cells, which have many stem-cell-like characteristics. They then used these cells — which have the same molecular signatures as cancer stem cells and are equally drug resistant — to screen around 16,000 chemicals. They found 32 contenders, then whittled the list down to one drug: salinomycin, an antibiotic often found in animal feed.