Truncated androgen receptor splice variants in prostate cancer

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.