Androgens as therapy for androgen receptor-positive castration-resistant prostate cancer

J Biomed Sci. 2011 Aug 23;18(1):63. doi: 10.1186/1423-0127-18-63.

Abstract

Prostate cancer is the most frequently diagnosed non-cutaneous tumor of men in Western countries. While surgery is often successful for organ-confined prostate cancer, androgen ablation therapy is the primary treatment for metastatic prostate cancer. However, this therapy is associated with several undesired side-effects, including increased risk of cardiovascular diseases. Shortening the period of androgen ablation therapy may benefit prostate cancer patients. Intermittent Androgen Deprivation therapy improves quality of life, reduces toxicity and medical costs, and delays disease progression in some patients. Cell culture and xenograft studies using androgen receptor (AR)-positive castration-resistant human prostate cancers cells (LNCaP, ARCaP, and PC-3 cells over-expressing AR) suggest that androgens may suppress the growth of AR-rich prostate cancer cells. Androgens cause growth inhibition and G1 cell cycle arrest in these cells by regulating c-Myc, Skp2, and p27Kip via AR. Higher dosages of testosterone cause greater growth inhibition of relapsed tumors. Manipulating androgen/AR signaling may therefore be a potential therapy for AR-positive advanced prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Cyclin-Dependent Kinase Inhibitor p27 / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • G1 Phase Cell Cycle Checkpoints / drug effects*
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • Prostatic Neoplasms / drug therapy*
  • Proto-Oncogene Proteins c-myc / metabolism
  • Receptors, Androgen / metabolism*
  • S-Phase Kinase-Associated Proteins / metabolism
  • Signal Transduction / drug effects*
  • Testosterone / pharmacology*
  • Testosterone / therapeutic use

Substances

  • MYC protein, human
  • Proto-Oncogene Proteins c-myc
  • Receptors, Androgen
  • S-Phase Kinase-Associated Proteins
  • Cyclin-Dependent Kinase Inhibitor p27
  • Testosterone