Importance of the field: The endothelin (ET) axis, which includes the biological
functions of ETs and their receptors, has played a physiological role in
normal tissue, acting as a modulator of vasomotor tone, tissue differentiation
and development, cell proliferation and hormone production. Interestingly, it
also functions in the growth and progression of various tumors. Several
researchers have identified the blockade of the ET-1 receptor as a promising
therapeutic approach.
Areas covered in this review: The clinical investigation of an orally bioavailable
ET antagonist, atrasentan, in prostate cancer, is encouraging. In this
neoplasia, it has shown antitumor activity, bone metastasis control and
amelioration of cancer-related pain but improvement in time to progression
and overall survival has still not been demonstrated. The clinical trials of other
ET antagonists are reported. Literature research was performed by Pubmed
and Pharmaprojects.
What the reader will gain: A comprehensive view about the use of atrasentan
in the treatment of castration-resistant prostate cancer (CRPC) is provided
together with the scientific rationale based on the function of ET and its
receptor in various cancer development mechanisms.
Take home message: Atrasentan seems to be active in CRPC, although
strong scientific evidence is still to be found. Interesting clinical findings
regard zibotentan
