The deadly poison made famous in countless Agatha Christie mysteries isn't known for its health benefits. But an arsenic compound has helped treat leukemia sufferers for over a decade, and we've just discovered it can fight other cancers as well.


The specific compound is arsenic trioxide, and it's already been approved by the FDA for the treatment of humans. The arsenic is combined with other therapies to fight cancers brought on by an error in a cellular signaling pathway known as the Hedgehog pathway. This signaling cascade regulates embryonic development and remains crucial to properly functioning cells in adults. Malfunctions in the Hedgehog pathway have been shown to cause tumors in the skin, brain, blood, and muscle.

Arsenic trioxide works in relatively low quantities by blocking one of the final steps in the Hedgehog pathway, preventing a few of the cell's genes being expressed that would otherwise cause runaway, cancerous growth. Other treatments currently on the market also target the Hedgehog pathway, but they do so at much earlier points in the signaling cascade. That gives the malfunctioning pathway many more opportunities to mutate around the drug and relay its self-destructive messages to the cells. The arsenic treatment takes effect so late in the pathway that's there is nearly no chance for the cancer to mutate around it.


Researchers Philip Beachy and Jynho Kim at the Stanford medical school first became interested in arsenic as a treatment for cancer when they noticed that birth defects brought on by arsenic exposure are very similar to the physical effects of not having an active Hedgehog pathway. They found that the same small amounts of arsenic trioxide that treated leukemia patients could also shut off the Hedgehog pathway, providing a potential treatment for sufferers of many other kinds of cancer.

Arsenic trioxide works by inhibiting a protein called Gli2 from causing gene transcription in the cell nucleus. Without Gli2, the Hedgehog pathway comes to a sudden, ineffectual end. Early tests of this treatment on mice found that most tumors either slowed down or stopped growing completely. Best of all, this works even in cells that have already proven resistant to other drugs that target the Hedgehog pathway.

[Proceedings of the National Academy of Sciences]