Anti-endothelin drugs in solid tumors.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
Atrasentan seems to be active in CRPC, although strong scientific evidence is still to be found. Interesting clinical findings regard zibotentan.
Russo
Antonio
A
Università di Palermo, Section of Medical Oncology, Department of Surgical and Oncological Sciences, Via del Vespro 129, 90127 Palermo, Italy. lab-oncobiologia@usa.net
Bronte
Giuseppe
G
Rizzo
Sergio
S
Fanale
Daniele
D
Di Gaudio
Francesca
F
Gebbia
Nicola
N
Bazan
Viviana
V
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use*; D000077868:Atrasentan; D016503:Drug Delivery Systems / Q000379:methods; D015507:Drugs, Investigational / Q000494:pharmacology / Q000627:therapeutic use*; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000037:antagonists & inhibitors* / Q000502:physiology; D006801:Humans; D008297:Male; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D011759:Pyrrolidines / Q000494:pharmacology / Q000627:therapeutic use*; D017466:Receptors, Endothelin / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects
D015507:Drugs, Investigational; D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D011759:Pyrrolidines; D017466:Receptors, Endothelin; D000077868:Atrasentan