Anti-endothelin drugs in solid tumors

Importance of the field: The endothelin (ET) axis, which includes the biologicalfunctions of ETs and their receptors, has played a physiological role innormal tissue, acting as a modulator of vasomotor tone, tissue differentiationand development, cell proliferation and hormone production. Interestingly, italso functions in the growth and progression of various tumors. Severalresearchers have identified the blockade of the ET-1 receptor as a promisingtherapeutic approach.Areas covered in this review: The clinical investigation of an orally bioavailableET antagonist, atrasentan, in prostate cancer, is encouraging. In thisneoplasia, it has shown antitumor activity, bone metastasis control andamelioration of cancer-related pain but improvement in time to progressionand overall survival has still not been demonstrated. The clinical trials of otherET antagonists are reported. Literature research was performed by Pubmedand Pharmaprojects.What the reader will gain: A comprehensive view about the use of atrasentanin the treatment of castration-resistant prostate cancer (CRPC) is providedtogether with the scientific rationale based on the function of ET and itsreceptor in various cancer development mechanisms.Take home message: Atrasentan seems to be active in CRPC, althoughstrong scientific evidence is still to be found. Interesting clinical findingsregard zibotentan.