Salinomycin potent against cancer stem cells in breast cancer

A multi-institutional team of Boston-area researchers has discovered a chemical salinomycin that works in mice to kill the rare but aggressive cells within breast cancers that have the ability to seed new tumors.

These cells, known as cancer stem cells, are thought to enable cancers to spread – and to reemerge after seemingly successful treatment. Although further work is needed to determine whether this specific chemical salinomycin holds therapeutic promise for humans, the study shows that it is possible to find chemicals that selectively kill cancer stem cells.

The scientists’ findings appear in the August 13 advance online issue of Cell.

“Evidence is accumulating rapidly that cancer stem cells are responsible for the aggressive powers of many tumors,” says Robert Weinberg, a Member of Whitehead Institute for Biomedical Research and one of the authors of the study.

An emerging idea in cancer biology is that tumors (breast, prostate, colon, lung, etc.) harbor a group of cells with the unique ability to regenerate cancers. In addition to promoting tumor growth, these so-called cancer stem cells are largely resistant to current cancer therapies. If it were possible to identify chemicals that selectively kill cancer stem cells, such chemicals might become critical candidates for future drug development.

The compound, called salinomycin, kills not only laboratory-created cancer stem cells, but also naturally occurring ones. Compared to a common chemotherapeutic drug prescribed for breast cancer (known as paclitaxel), salinomycin reduced the number of cancer stem cells by more than 100-fold. It also diminished breast tumor growth in mice.

To further dissect the function of salinomycin, the researchers also examined its genetic effects. Previous studies of tumors from breast cancer patients have revealed groups of genes that are highly active in cancer stem cells. Many of these same genes are linked with particularly aggressive tumors and poor patient prognoses. The researchers’ studies show that salinomycin (but not paclitaxel) treatment can decrease the activity of these genes, revealing a possible molecular basis for the chemical’s biological effects.

“Our work reveals the biological effects of targeting cancer stem cells,” says co-first author Piyush Gupta, a researcher at the Broad Institute. “Moreover, it suggests a general approach to finding novel anti-cancer therapies that can be applied to any solid tumor maintained by cancer stem cells.”

Although the new findings signal a noteworthy scientific milestone, it is still too early to know whether cancer patients will reap benefits from it. Additional research is needed to determine exactly how salinomycin works to kill cancer stem cells and if it can wield the same tumor-reducing power in humans as it does in mice. These types of analyses generally take several years to complete.

Source: Whitehead Institute for Biomedical Research, USA



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