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An Orthotopic Murine Model of Human Prostate Cancer Metastasis
06:48

An Orthotopic Murine Model of Human Prostate Cancer Metastasis

Published on: September 18, 2013

Targeting bone metastasis in prostate cancer with endothelin receptor antagonists

Michael A Carducci1, Antonio Jimeno

  • 1Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland 21231-1000, USA. carducci@jhmi.edu

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|October 26, 2006
PubMed

Insights

Endothelin receptor antagonists, like atrasentan, show promise in targeting prostate cancer bone metastasis by inhibiting tumor cell proliferation and bone remodeling. Clinical trials indicate a delay in disease progression, particularly in patients with bone involvement.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Prostate cancer bone metastasis involves complex interactions between tumor cells and the bone microenvironment.
  • Endothelin (ET) signaling, particularly via the ETA receptor, plays a significant role in prostate cancer progression and bone metastasis.
  • ET-1 contributes to tumor cell proliferation, apoptosis resistance, invasion, and bone remodeling, impacting pain modulation.

Purpose of the Study:

  • To evaluate the potential of targeting the Endothelin axis for treating prostate cancer bone metastasis.
  • To assess the biological and clinical activity of atrasentan (ABT-627), an ETA receptor antagonist, in prostate cancer patients.

Main Methods:

  • Clinical evaluation of atrasentan in patients with prostate cancer, particularly hormone-refractory cases.
  • Monitoring of biochemical markers of prostate cancer progression in bone.
  • Assessment of time to disease progression compared to placebo in patients with bone metastases.

Main Results:

  • Atrasentan demonstrated biological activity by suppressing biochemical markers of prostate cancer progression in bone.
  • Clinical activity showed a trend towards delaying disease progression compared to placebo.
  • The delay in progression was more pronounced in patients with bone metastases.

Conclusions:

  • Targeting the Endothelin axis, specifically ETA receptors, is a viable therapeutic strategy for prostate cancer bone metastasis.
  • Atrasentan exhibits promising biological and clinical activity, warranting further investigation.
  • Ongoing studies with atrasentan and other ET-1 antagonists like ZD4054 are crucial for advancing treatment options.

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