ANDROGEN RECEPTOR GENE AMPLIFICATION - A NOVEL MOLECULAR MECHANISM FOR ENDOCRINE THERAPY RESISTANCE IN HUMAN PROSTATE-CANCER

Since the development and growth of the prostate cancer is highly depe ndent on androgens, androgen deprivation therapy continues to be the t reatment of choice for patients with advanced prostate cancer. The the rapy is very effective, but responses are often short-lived. We descri be here a novel molecular mechanism that may explain why prostate canc er cells become resistant to hormonal therapy. Amplification of the an drogen receptor (AR) gene was found to be selected for during androgen deprivation therapy in 23% of prostate cancer patients who experience d local tumor recurrence. Amplification leads to increased expression of the AR gene, which enables the cancer cells to more effectively uti lize the residual low levels of androgens for sustaining cell growth. Discovery of AR amplification as a possible molecular mechanism of the rapy resistance in prostate cancer should prove useful for development of more effective endocrine therapy regimens as well as diagnostic an d predictive tests for therapy failure.