Endothelin-1 and Its Role in Cancer and Potential Therapeutic Opportunities.

ABSTRACT

Endothelin-1 (ET-1) plays a physiological role as a potent vasoconstrictor. It is implicated in an array of diseases, and its signalling is often found to be overactivated within cancers. ET-1 has been found to potentiate hallmarks of cancer progression such as cell proliferation, invasion and metastasis, as well as angiogenesis. ET-1 has also been implicated in inducing the epithelial-mesenchymal transition (EMT) and promoting resistance to anticancer drugs. Many preclinical efforts have been made to target ET-1 expression within cancer, such as by using ET-1 receptor antagonists, many of which have been approved for treating pulmonary hypertension. Targeting ET-1 has been shown to improve the response to various other cancer therapeutics, highlighting the potential benefits targeting this peptide may exert. Drug repurposing is an attractive strategy, and exploration of this avenue may be promising for targeting ET-1 in cancer. There are many clinical trials which have been completed and are currently undergoing involving the repurposing of ET-1 receptor antagonists for cancer treatment. In this review, the pathways through which ET-1 potentiates cancer will be discussed, as well as where the opportunity for therapeutic intervention lies in relation to cancer.