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Endothelin receptor antagonists

Joel B Nelson1

  • 1Department of Urology, University of Pittsburgh School of Medicine, 5200 Centre Ave, Suite 209, Pittsburgh, PA 15232, USA. nelsonjb@upmc.edu

World Journal of Urology
|January 18, 2005
PubMed

Insights

New therapies targeting the endothelin axis show promise for hormone refractory prostate cancer. Atrasentan, an endothelin receptor A antagonist, delayed disease progression in clinical trials, potentially managing advanced prostate cancer.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Hormone refractory prostate cancer (HRPC) progression is difficult to manage.
  • Novel therapeutic targets are needed for HRPC.
  • The endothelin axis is implicated in prostate cancer progression.

Purpose of the Study:

  • To review the role of the endothelin axis in prostate cancer.
  • To discuss preclinical data supporting endothelin receptor antagonists.
  • To present clinical trial findings for atrasentan in HRPC.

Main Methods:

  • Literature review of endothelin axis in cancer.
  • Analysis of preclinical studies on endothelin signaling.
  • Summary of Phase II and III clinical trial data for atrasentan.

Main Results:

  • The endothelin axis is a viable therapeutic target in prostate cancer.
  • Atrasentan, an endothelin receptor A (ET(A)) antagonist, demonstrated efficacy.
  • Disease progression was delayed in some patients with advanced prostate cancer treated with atrasentan.
  • Atrasentan was well tolerated and is an oral agent.

Conclusions:

  • Targeting the endothelin axis, specifically ET(A) receptors, offers a new therapeutic strategy for HRPC.
  • Atrasentan shows potential to manage advanced prostate cancer, possibly converting it to a more chronic condition.
  • Further investigation into atrasentan and the endothelin axis is warranted for HRPC treatment.

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