Hedgehog signaling in basal cell carcinoma

J Dermatol Sci. 2015 May;78(2):95-100. doi: 10.1016/j.jdermsci.2015.02.007. Epub 2015 Feb 23.

Abstract

Basal cell carcinoma (BCC), the most common type of skin cancer, is occasionally aggressive with deep invasion, destruction of adjacent structures, recurrence and, on very rare occasions, regional and distant metastases. Mutations that occur in BCC in hedgehog (Hh) pathway genes primarily involve the genes encoding patched homolog (PTCH) and smoothened homolog (SMO). Several animal models have demonstrated the functional relevance of genetic alterations in the Hh pathway during tumorigenesis. Recently, targeted therapy has become available both commercially and in the context of human clinical trials. Interestingly, Hh pathway inhibitors not only suppress BCC progression but also promote acquired immune responses. Since immune responses are crucial for long-term tumor control, new clinical trials, such as those involving a combination of Hh inhibitors with immune modifiers, are needed to supplement standard methods of tumor control.

Keywords: Acquired immune responses; Basal cell carcinoma; Hedgehog.

Publication types

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

MeSH terms

  • Adaptive Immunity / drug effects
  • Anilides / therapeutic use
  • Animals
  • Antineoplastic Agents / therapeutic use
  • Carcinoma, Basal Cell / drug therapy*
  • Carcinoma, Basal Cell / genetics
  • Carcinoma, Basal Cell / metabolism*
  • Hedgehog Proteins / antagonists & inhibitors
  • Hedgehog Proteins / genetics
  • Hedgehog Proteins / metabolism*
  • Humans
  • Molecular Targeted Therapy
  • Patched Receptors
  • Patched-1 Receptor
  • Pyridines / therapeutic use
  • Receptors, Cell Surface / metabolism
  • Receptors, G-Protein-Coupled / antagonists & inhibitors
  • Receptors, G-Protein-Coupled / metabolism
  • Signal Transduction*
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / genetics
  • Skin Neoplasms / metabolism*
  • Smoothened Receptor

Substances

  • Anilides
  • Antineoplastic Agents
  • Hedgehog Proteins
  • HhAntag691
  • PTCH1 protein, human
  • Patched Receptors
  • Patched-1 Receptor
  • Pyridines
  • Receptors, Cell Surface
  • Receptors, G-Protein-Coupled
  • SMO protein, human
  • Smoothened Receptor