Mechanisms of androgen resistance in prostate cancer

Prostate tumors, although initially androgen dependent, inevitably progress to a hormone-independent phenotype after treatment with androgen deprivati on, This change in phenotype is a result of the selective growth of androge n-independent cells already present at the initiation of therapy. The exact mechanism by which an androgen-resistant cell develops is unknown. Potenti al mechanisms involve alterations of the androgen receptor, gene amplificat ion, altered signaling pathways, or aberrant expression of growth factors, None of these alterations has been demonstrated universally in androgen-res istant tumors. Most likely, it is the accumulation, as well as yet to be de scribed synergism, of multiple genetic alterations that leads to the androg en-resistant phenotype.