The Hedgehog pathway as a therapeutic target

Summary

The Hedgehog pathway is inactive in most normal adult tissues.¹ The inappropriate activation of Hedgehog signaling in certain cancers suggests that this pathway could be a potential therapeutic target for treatment of cancer patients.² Due to teratogenic effects in animals, natural inhibitors of the Hedgehog pathway were identified almost 50 years ago, long before discovery of the pathway.³ These compounds were later found to inhibit the Hedgehog pathway’s Smoothened (SMO) protein.^4,5 Efforts are being made to develop novel synthetic inhibitors of SMO with improved pharmaceutical properties.⁶ Other potential therapeutic targets include the Hedgehog ligands and the Gli transcription factors.⁷