The endothelin axis in cancer: the promise and the challenges of molecularly targeted therapy

Can J Physiol Pharmacol. 2008 Aug;86(8):473-84. doi: 10.1139/Y08-058.


The endothelin (ET) axis, which includes ET-1, ET-2, ET-3, and 2 G protein-coupled receptor subtypes, ET AR and ET BR, promotes growth and progression of a variety of tumors, such as prostatic, ovarian, renal, pulmonary, colorectal, cervical, breast, lung, bladder, endometrial carcinoma, Kaposi's sarcoma, brain tumors, and melanoma. Acting on selective receptors, ET-1 regulates mitogenesis, cell survival, angiogenesis, bone remodeling, stimulation of nociceptors, tumor-infiltrating immune cells, epithelial-to-mesenchymal transition, invasion, and metastatic dissemination. At the molecular level, endothelin receptor antagonists, besides providing ideal tools for dissecting the ET axis, have demonstrated their potential in developing novel therapeutic strategies. Emerging experimental and clinical data demonstrate that interfering with endothelin receptors provides an opportunity for the development of rational combinatorial approaches using endothelin receptor antagonists in combination with chemotherapy or molecularly targeted therapy.

Publication types

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

MeSH terms

  • Angiogenesis Inhibitors / pharmacology
  • Angiogenesis Inhibitors / therapeutic use
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Endothelin-1 / biosynthesis
  • Endothelins / genetics*
  • Endothelins / physiology
  • Humans
  • Neoplasms / drug therapy*
  • Neoplasms / genetics*
  • Neovascularization, Pathologic / drug therapy
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / pathology
  • Receptors, Endothelin / drug effects
  • Receptors, Endothelin / genetics
  • Receptors, Endothelin / physiology
  • Signal Transduction


  • Angiogenesis Inhibitors
  • Antineoplastic Agents
  • Endothelin-1
  • Endothelins
  • Receptors, Endothelin