Therapeutic Inhibition of Hedgehog-GLI Signaling in Cancer: Epithelial, Stromal, or Stem Cell Targets?

Hedgehog (HH)-GLI signaling is a developmental patterning pathway used by many tumors for bulk proliferation that has been shown also to regulate cancer stem cell self-renewal and survival. Surprisingly, a recent study by Yauch et al. (2008) proposes that HH-GLI signaling acts only on the tumor stroma. The mode of action of HH-GLI signaling in cancer may shape the development of therapeutic antagonists.