Hedgehog Signaling: From Basic Biology to Cancer Therapy

Cell Chem Biol. 2017 Mar 16;24(3):252-280. doi: 10.1016/j.chembiol.2017.02.010. Epub 2017 Mar 9.


The Hedgehog (HH) signaling pathway was discovered originally as a key pathway in embryonic patterning and development. Since its discovery, it has become increasingly clear that the HH pathway also plays important roles in a multitude of cancers. Therefore, HH signaling has emerged as a therapeutic target of interest for cancer therapy. In this review, we provide a brief overview of HH signaling and the key molecular players involved and offer an up-to-date summary of our current knowledge of endogenous and exogenous small molecules that modulate HH signaling. We discuss experiences and lessons learned from the decades-long efforts toward the development of cancer therapies targeting the HH pathway. Challenges to develop next-generation cancer therapies are highlighted.

Keywords: GLI; basal cell carcinoma; cancer therapy; cholesterol; drug resistance; endogenous smoothened regulation; hedgehog signaling; medulloblastoma; smoothened; stem cell.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / therapeutic use
  • Cilia / metabolism
  • Hedgehog Proteins / antagonists & inhibitors
  • Hedgehog Proteins / chemistry
  • Hedgehog Proteins / metabolism*
  • Humans
  • Kruppel-Like Transcription Factors / metabolism
  • Neoplasms / drug therapy
  • Neoplasms / metabolism
  • Neoplasms / pathology*
  • Oxysterols / chemistry
  • Oxysterols / metabolism
  • Phosphatidylinositol Phosphates / chemistry
  • Phosphatidylinositol Phosphates / metabolism
  • Signal Transduction* / drug effects
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / metabolism
  • Small Molecule Libraries / pharmacology
  • Smoothened Receptor / agonists
  • Smoothened Receptor / antagonists & inhibitors
  • Smoothened Receptor / metabolism


  • Antineoplastic Agents
  • Hedgehog Proteins
  • Kruppel-Like Transcription Factors
  • Oxysterols
  • Phosphatidylinositol Phosphates
  • Small Molecule Libraries
  • Smoothened Receptor
  • phosphatidylinositol 4-phosphate