Hedgehog signaling pathway as a target for therapeutic intervention in basal cell carcinoma

Drug News Perspect. 2003 Dec;16(10):657-62. doi: 10.1358/dnp.2003.16.10.829296.

Abstract

Basal cell carcinomas (BCC) are slow-growing skin tumors that rarely metastasize but frequently recur, most often around the face, head and neck. Currently, surgery is the only treatment practice, which can be painful and leave scars. However, several years ago it was discovered that almost all forms of BCC result from mutations in a signaling pathway controlled by a protein called Hedgehog (Hh). Recently, a novel small-molecule drug candidate, CUR-61414, has been identified that blocks this pathway and could potentially be effective for the treatment of BCC. CUR-61414 was reported to prevent the proliferation and selectively induce the death of the tumor cells, while not harming adjacent normal skin cells in two different models of BCC. These findings directly demonstrate that the use of Hh inhibitors could be a valid novel therapeutic approach for treating BCC.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Carcinoma, Basal Cell / drug therapy
  • Carcinoma, Basal Cell / metabolism*
  • Carcinoma, Basal Cell / pathology
  • Carrier Proteins / antagonists & inhibitors
  • Carrier Proteins / metabolism*
  • Carrier Proteins / physiology
  • Dioxoles / adverse effects
  • Dioxoles / pharmacology
  • Dioxoles / therapeutic use
  • Humans
  • Membrane Glycoproteins / antagonists & inhibitors
  • Membrane Glycoproteins / metabolism*
  • Membrane Glycoproteins / physiology
  • Mutation
  • Piperazines / adverse effects
  • Piperazines / pharmacology
  • Piperazines / therapeutic use
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Skin Neoplasms / drug therapy
  • Skin Neoplasms / metabolism*
  • Skin Neoplasms / pathology

Substances

  • Antineoplastic Agents
  • CUR 61414
  • Carrier Proteins
  • Dioxoles
  • HHIP protein, human
  • Membrane Glycoproteins
  • Piperazines