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The androgen receptor in hormone-refractory prostate cancer

Hai-Lei Mao1, Zhi-Qi Zhu, Charlie Degui Chen

  • 1State Key Laboratory of Molecular Biology, Shanghai Key Laboratory of Andrology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.

Asian Journal of Andrology
|December 4, 2008
PubMed

Insights

Advanced prostate cancer initially responds to hormone therapy targeting androgen receptor (AR) signaling. However, tumors often become hormone-refractory (HR), yet AR remains crucial, suggesting new AR-targeted therapies for HR prostate cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Urology

Background:

  • Advanced prostate cancer is initially sensitive to androgen receptor (AR) targeted hormone therapy.
  • Tumors frequently develop hormone-refractory (HR) prostate cancer, a lethal stage where standard therapies fail.
  • Despite resistance, AR signaling remains active and essential in HR prostate cancer.

Purpose of the Study:

  • To investigate the continued role of AR signaling in hormone-refractory prostate cancer.
  • To explore mechanisms by which AR signaling is reactivated or maintained in HRPC.
  • To evaluate the potential of targeting AR signaling for HRPC treatment.

Main Methods:

  • Review of current literature on AR signaling in prostate cancer.
  • Analysis of mechanisms driving AR reactivation in hormone-refractory tumors.
  • Discussion of therapeutic strategies targeting AR in HRPC.

Main Results:

  • AR signaling persists in HRPC through various mechanisms.
  • Intracellular pathways can sensitize AR to low androgen levels.
  • AR mutations can alter ligand specificity, activating it with non-steroidal compounds.
  • AR overexpression enhances sensitivity to low androgen concentrations.

Conclusions:

  • The androgen receptor (AR) remains a viable therapeutic target in hormone-refractory prostate cancer (HRPC).
  • Understanding AR reactivation pathways is key to developing effective HRPC treatments.
  • Targeting AR signaling pathways offers a promising strategy for advanced, refractory prostate cancer.

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