Role of the endothelin axis and its antagonists in the treatment of cancer

A. Bagnato, M. Loizidou, Beth Pflug, J. Curwen, J. Growcott

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

The endothelins (ET) are a group of proteins that act through G-protein coupled receptors. Endothelin-1 (ET-1) was initially identified as a potent vasoconstrictor and dysregulation of the ET axis contributes to pathological processes responsible for cardiovascular disease states. More recently, the ET axis, in particular ET-1 acting through the endothelin A receptor (ET A), has been implicated in the development of several cancers through activation of pathways involved in cell proliferation, migration, invasion, epithelial-mesenchymal transition, osteogenesis and angiogenesis. The endothelin B receptor (ET B) may counter tumour progression by promoting apoptosis and clearing ET-1; however, it has recently been implicated in the development of some tumour types including melanomas and oligodendrogliomas. Here, we review emerging preclinical and clinical data outlining the role of the ET axis in cancer, and its antagonism as an attractive and challenging approach to improve clinical cancer management. Clinical data of ET A antagonists in patients with prostate cancer are encouraging and provide promise for new ET A antagonist-based treatment strategies. Given the unexpected opportunities to affect pleiotrophic tumorigenic signals by targeting ET A-mediated pathways in a number of cancers, the evaluation of ET-targeted therapy in cancer warrants further investigation.

Original languageEnglish
Pages (from-to)220-233
Number of pages14
JournalBritish Journal of Pharmacology
Volume163
Issue number2
DOIs
StatePublished - May 2011

Fingerprint

Endothelins
Endothelin-1
Neoplasms
Therapeutics
Endothelin B Receptors
Oligodendroglioma
Endothelin A Receptors
Epithelial-Mesenchymal Transition
Vasoconstrictor Agents
Pathologic Processes
G-Protein-Coupled Receptors
Osteogenesis
Cell Movement
Melanoma
Prostatic Neoplasms
Cardiovascular Diseases
Cell Proliferation
Apoptosis
Proteins

Keywords

  • cancer
  • endothelin
  • endothelin antagonist
  • endothelin receptor
  • ET receptor
  • ET receptor
  • GPCR
  • zibotentan

ASJC Scopus subject areas

  • Pharmacology

Cite this

Role of the endothelin axis and its antagonists in the treatment of cancer. / Bagnato, A.; Loizidou, M.; Pflug, Beth; Curwen, J.; Growcott, J.

In: British Journal of Pharmacology, Vol. 163, No. 2, 05.2011, p. 220-233.

Research output: Contribution to journalArticle

Bagnato, A. ; Loizidou, M. ; Pflug, Beth ; Curwen, J. ; Growcott, J. / Role of the endothelin axis and its antagonists in the treatment of cancer. In: British Journal of Pharmacology. 2011 ; Vol. 163, No. 2. pp. 220-233.
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