Basal Cell Carcinomas: Attack of the Hedgehog

Nat Rev Cancer. 2008 Oct;8(10):743-54. doi: 10.1038/nrc2503.

Abstract

Basal cell carcinomas (BCCs) were essentially a molecular 'black box' until some 12 years ago, when identification of a genetic flaw in a rare subset of patients who have a great propensity to develop BCCs pointed to aberrant Hedgehog signalling as the pivotal defect leading to formation of these tumours. This discovery has facilitated a remarkable increase in our understanding of BCC carcinogenesis and has highlighted the carcinogenic role of this developmental pathway when aberrantly activated in adulthood. Importantly, a phase 1 first-in-human trial of a Hedgehog inhibitor has shown real progress in halting and even reversing the growth of these tumours.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use
  • Basal Cell Nevus Syndrome / genetics
  • Basal Cell Nevus Syndrome / physiopathology
  • Carcinoma, Basal Cell / drug therapy
  • Carcinoma, Basal Cell / epidemiology
  • Carcinoma, Basal Cell / genetics
  • Carcinoma, Basal Cell / metabolism*
  • Genetic Predisposition to Disease
  • Hedgehog Proteins / antagonists & inhibitors
  • Hedgehog Proteins / genetics
  • Hedgehog Proteins / metabolism*
  • Humans
  • Mice
  • Patched Receptors
  • Receptors, Cell Surface / genetics
  • Signal Transduction / drug effects
  • Skin Neoplasms / drug therapy
  • Skin Neoplasms / epidemiology
  • Skin Neoplasms / genetics
  • Skin Neoplasms / metabolism*
  • United States / epidemiology

Substances

  • Antineoplastic Agents
  • Hedgehog Proteins
  • Patched Receptors
  • Receptors, Cell Surface