Unraveling the therapeutic potential of the Hedgehog pathway in cancer

Nat Med. 2013 Nov;19(11):1410-22. doi: 10.1038/nm.3389. Epub 2013 Nov 7.

Abstract

Major progress has been made in recent years in the development of Hedgehog (Hh) pathway inhibitors for the treatment of patients with cancer. Promising clinical trial results have been obtained in cancers that harbor activating mutations of the Hh pathway, such as basal cell carcinoma and medulloblastoma. However, for many cancers, in which Hh ligand overexpression is thought to drive tumor growth, results have been disappointing. Here we review the preclinical data that continue to shape our understanding of the Hh pathway in tumorigenesis and the emerging clinical experience with smoothened inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols
  • Drug Discovery
  • Drug Resistance, Neoplasm / genetics
  • Hedgehog Proteins / antagonists & inhibitors*
  • Hedgehog Proteins / genetics
  • Hedgehog Proteins / metabolism*
  • Humans
  • Ligands
  • Models, Biological
  • Molecular Targeted Therapy
  • Mutation
  • Neoplasms / drug therapy*
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Neoplastic Stem Cells / drug effects
  • Neoplastic Stem Cells / metabolism
  • Receptors, G-Protein-Coupled / antagonists & inhibitors
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism
  • Signal Transduction
  • Smoothened Receptor
  • Transcription Factors / metabolism
  • Translational Medical Research
  • Zinc Finger Protein GLI1

Substances

  • GLI1 protein, human
  • Hedgehog Proteins
  • Ligands
  • Receptors, G-Protein-Coupled
  • SMO protein, human
  • Smoothened Receptor
  • Transcription Factors
  • Zinc Finger Protein GLI1