Molecular Alterations during Progression of Prostate Cancer to Androgen Independence

BACKGROUND: Prostate cancer is the most commonly diagnosed cancer among men in North America and is a leading cause of death. Standard treatments include androgen deprivation therapy, which leads to improved clinical outcomes. However, over time, most tumors become androgen independent and no longer respond to hormonal therapies. Several mechanisms have been implicated in the progression of prostate cancer to androgen independence. CONTENT: Most tumors that have become androgen independent still rely on androgen receptor (AR) signaling. Mechanisms that enhance AR signaling in androgen-depleted conditions include: AR gene amplification, AR mutations, changes in the balance of AR cofactors, increases in steroidogenic precursors, and activation via outlaw pathways. Along with AR signaling, various other AR-independent bypass pathways have been shown to operate aberrantly during androgen independence. Changes in the epigenetic signatures and microRNA concentrations have also been implicated in the development of androgenindependent prostate cancer. SUMMARY: Understanding of the molecular mechanisms that lead to the development of androgenindependent prostate cancer will allow for improved therapeutic strategies that target key pathways and molecules that are essential for these cells to survive. (C) 2011 American Association for Clinical Chemistry