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Arsenic against the hedgehog

Researchers at the Stanford University School of Medicine have found that arsenic trioxide is able to antagonize the hedgehog pathway.1 The findings could open up hedgehog-driven solid tumors such as basal cell carcinoma and medulloblastoma as new indications for Cephalon Inc.'s Trisenox arsenic trioxide, which already is marketed for acute promyelocytic leukemia, a form of blood cancer.

Aberrant activation of the hedgehog (Hh) pathway can result from loss-of-function mutations in patched 1 (PTCH1), which is an inhibitory cell surface receptor in the pathway, through activating mutations in smoothened(SMO), which is a membrane component downstream of PTCH1, or in intracellular pathway components downstream of SMO.2 Although a handful of biotechs are attacking SMO, a team led by Philip Beachy, a professor of developmental biology at Stanford and a member of the university's Institute for Stem Cell Biology and Regenerative Medicine, has been searching for ways to block downstream targets.

Beachy and colleagues decided to test arsenic trioxide (ATO) because arsenic-containing compounds are known to cause embryonic defects associated

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