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Role of the endothelin axis and its antagonists in the treatment of cancer
Author(s) -
Bagnato A,
Loizidou M,
Pflug BR,
Curwen J,
Growcott J
Publication year - 2011
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2011.01217.x
Subject(s) - endothelins , endothelin 3 , endothelin receptor , medicine , cancer research , prostate cancer , cancer , angiogenesis , receptor , bioinformatics , biology
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.