Sonic Hedgehog in pancreatic cancer: from bench to bedside, then back to the bench

Surgery. 2012 Sep;152(3 Suppl 1):S19-32. doi: 10.1016/j.surg.2012.05.030. Epub 2012 Jul 6.


Developmental genes are known to regulate cell proliferation, migration, and differentiation; thus, it comes as no surprise that the misregulation of developmental genes plays an important role in the biology of human cancers. One such pathway that has received an increasing amount of attention for its function in carcinogenesis is the Hedgehog (Hh) pathway. Initially the domain of developmental biologists, the Hh pathway and one of its ligands, Sonic Hedgehog (Shh), have been shown to play an important role in body planning and organ development, particularly in the foregut endoderm. Their importance in human disease became known to cancer biologists when germline mutations that resulted in the unregulated activity of the Hh pathway were found to cause basal cell carcinoma and medulloblastoma. Since then, misexpression of the Hh pathway has been shown to play an important role in many other cancers, including those of the pancreas. In many institutions, investigators are targeting misexpression of the Hh pathway in clinical trials, but there is still much fundamental knowledge to be gained about this pathway that can shape its clinical utility. This review will outline the evolution of our understanding of this pathway as it relates to the pancreas, as well as how the Hh pathway came to be a high-priority target for treatment.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Hedgehog Proteins / antagonists & inhibitors
  • Hedgehog Proteins / physiology*
  • Humans
  • Inflammation
  • Metaplasia
  • Neoplasm Metastasis / physiopathology
  • Pancreas / growth & development
  • Pancreas / injuries
  • Pancreatic Neoplasms / drug therapy
  • Pancreatic Neoplasms / physiopathology*
  • Receptors, G-Protein-Coupled / antagonists & inhibitors
  • Receptors, G-Protein-Coupled / physiology
  • Regeneration / physiology
  • Signal Transduction
  • Smoothened Receptor
  • Up-Regulation


  • Hedgehog Proteins
  • Receptors, G-Protein-Coupled
  • SMO protein, human
  • Smoothened Receptor