title: Anti-endothelin drugs in solid tumors.
abstract: 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.
authors.affiliation: Università di Palermo, Section of Medical Oncology, Department of Surgical and Oncological Sciences, Via del Vespro 129, 90127 Palermo, Italy. lab-oncobiologia@usa.net
authors.forename: Antonio
authors.initials: A
authors.lastname: Russo
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Bronte
authors.forename: Sergio
authors.initials: S
authors.lastname: Rizzo
authors.forename: Daniele
authors.initials: D
authors.lastname: Fanale
authors.forename: Francesca
authors.initials: F
authors.lastname: Di Gaudio
authors.forename: Nicola
authors.initials: N
authors.lastname: Gebbia
authors.forename: Viviana
authors.initials: V
authors.lastname: Bazan
mesh_terms: 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
chemical_list: D015507:Drugs, Investigational; D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D011759:Pyrrolidines; D017466:Receptors, Endothelin; D000077868:Atrasentan