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Anti-endothelin drugs in solid tumors.

AbstractIMPORTANCE 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.
AuthorsAntonio Russo, Giuseppe Bronte, Sergio Rizzo, Daniele Fanale, Francesca Di Gaudio, Nicola Gebbia, Viviana Bazan
JournalExpert opinion on emerging drugs (Expert Opin Emerg Drugs) Vol. 15 Issue 1 Pg. 27-40 (Mar 2010) ISSN: 1744-7623 [Electronic] England
PMID20102289 (Publication Type: Journal Article, Review)
Chemical References
  • Drugs, Investigational
  • Endothelin Receptor Antagonists
  • Endothelins
  • Pyrrolidines
  • Receptors, Endothelin
  • atrasentan
Topics
  • Antineoplastic Combined Chemotherapy Protocols (pharmacology, therapeutic use)
  • Drug Delivery Systems (methods)
  • Drugs, Investigational (pharmacology, therapeutic use)
  • Endothelin Receptor Antagonists
  • Endothelins (antagonists & inhibitors, physiology)
  • Humans
  • Male
  • Models, Biological
  • Neoplasms (drug therapy, physiopathology)
  • Prostatic Neoplasms (drug therapy)
  • Pyrrolidines (pharmacology, therapeutic use)
  • Receptors, Endothelin (physiology)
  • Signal Transduction (drug effects)

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