Androgen receptor signaling in androgen-refractory prostate cancer

Michael E. Grossmann, Haojie Huang, Donald J. Tindall

Research output: Contribution to journalArticle

447 Citations (Scopus)

Abstract

Prostate cancer is the second most prevalent cancer in males in the United States. Standard therapy relies on removing, or blocking the actions of, androgens. In most cases, this therapy results in a regression of the cancer because the prostate and most primary prostate tumors depend on androgens for growth and the avoidance of apoptosis. However, a portion of the cancers eventually relapse, at which point they are termed "androgen refractory" and can no longer be cured by conventional therapy of any type. The precise molecular events that lead from androgen-sensitive prostate cancer to androgen-refractory prostate cancer are, therefore, of great interest. This review seeks to identify specific molecular events that may be linked directly to the progression to androgen-refractory cancer. Some of the mechanisms appear to involve the androgen receptor (AR) directly and include mutations in, or amplification of, the AR gene in a manner that allows the AR to respond to low doses of androgens, other steroids, or antiandrogens. In a less direct manner, coactivators may increase the sensitivity of the AR to androgens and even other nonandrogenic substances through a number of mechanisms. Additional indirect mechanisms that do not result from mutation of the AR may involve activation of the AR by peptide growth factors or cytokines or may involve bypassing the AR entirely via other cellular pathways. Identification of the role of these mechanisms in the progression to androgen-refractory prostate cancer is critical for developing therapies capable of curing this disease.

Original languageEnglish (US)
Pages (from-to)1687-1697
Number of pages11
JournalJournal of the National Cancer Institute
Volume93
Issue number22
StatePublished - Nov 21 2001

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Androgen Receptors
Androgens
Prostatic Neoplasms
Neoplasms
Androgen Antagonists
Mutation
Therapeutics
Prostate
Intercellular Signaling Peptides and Proteins
Steroids
Apoptosis
Cytokines
Recurrence
Peptides
Growth

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Androgen receptor signaling in androgen-refractory prostate cancer. / Grossmann, Michael E.; Huang, Haojie; Tindall, Donald J.

In: Journal of the National Cancer Institute, Vol. 93, No. 22, 21.11.2001, p. 1687-1697.

Research output: Contribution to journalArticle

Grossmann, Michael E. ; Huang, Haojie ; Tindall, Donald J. / Androgen receptor signaling in androgen-refractory prostate cancer. In: Journal of the National Cancer Institute. 2001 ; Vol. 93, No. 22. pp. 1687-1697.
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