Dysregulated Hedgehog (Hh) signaling has been implicated in a growing number of human cancers. To date, most antagonists of this signaling pathway that have been developed target the Hh receptor Smoothened. However, these are predicted to have minimal effect when the pathway is activated as a result of dysregulation downstream of this receptor. In this issue of the JCI, Beauchamp and colleagues provide preclinical evidence that arsenic trioxide, a drug FDA approved for the treatment of acute promyelocytic leukemia, inhibits the growth of Ewing sarcoma and medulloblastoma cells by targeting GLI family zinc finger (GLI) proteins, which are Hh signaling pathway components downstream of Smoothened.
