The androgen receptor (AR) is fundamental for the growth and survival of normal and malignant prostate cells. Therefore, androgen deprivation therapy remains the first-line treatment for disseminated disease; however, relapse and progression to a castration-resistant phenotype for which no durable treatment currently exists, is inevitable. Restored AR activity is fundamental in the progression to castration-resistant prostate cancer. Multiple mechanisms by which AR is reactivated under androgen- depleted conditions may be involved in the development of this lethal phenotype. Recent studies have identified alternatively spliced transcripts encoding truncated AR isoforms that lack the ligand-binding domain, which is the therapeutic target of androgen deprivation therapy. Many of these truncated AR variants function as constitutively active, ligand-independent transcription factors that can support androgenindependent expression of AR target genes, as well as ligand-independent growth of prostate cancer cells. In this chapter, we will summarize the recent developments in the identification and characterization of AR splice variants in prostate cancer.
|Original language||English (US)|
|Title of host publication||Prostate Cancer|
|Subtitle of host publication||Biochemistry, Molecular Biology and Genetics|
|Publisher||Springer New York|
|Number of pages||32|
|State||Published - Jan 1 2013|
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