Koivisto P, Visakorpi T, Kallioniemi O P
Laboratory of Cancer Genetics, University of Tampere, Finland.
Scand J Clin Lab Invest Suppl. 1996;226:57-63.
Since the development and growth of the prostate cancer is highly dependent on androgens, androgen deprivation therapy continues to be the treatment of choice for patients with advanced prostate cancer. The therapy is very effective, but responses are often short-lived. We describe here a novel molecular mechanism that may explain why prostate cancer cells become resistant to hormonal therapy. Amplification of the androgen receptor (AR) gene was found to be selected for during androgen deprivation therapy in 23% of prostate cancer patients who experienced local tumor recurrence. Amplification leads to increased expression of the AR gene, which enables the cancer cells to more effectively utilize the residual low levels of androgens for sustaining cell growth. Discovery of AR amplification as a possible molecular mechanism of therapy resistance in prostate cancer should prove useful for development of more effective endocrine therapy regimens as well as diagnostic and predictive tests for therapy failure.
由于前列腺癌的发展和生长高度依赖雄激素，雄激素剥夺疗法仍然是晚期前列腺癌患者的首选治疗方法。该疗法非常有效，但反应往往是短暂的。我们在此描述一种新的分子机制，该机制可能解释前列腺癌细胞为何对激素疗法产生抗性。在经历局部肿瘤复发的23%的前列腺癌患者中，发现雄激素剥夺疗法期间雄激素受体（AR）基因发生了扩增。扩增导致AR基因表达增加，这使得癌细胞能够更有效地利用残留的低水平雄激素来维持细胞生长。发现AR扩增作为前列腺癌治疗抗性的一种可能分子机制，对于开发更有效的内分泌治疗方案以及治疗失败的诊断和预测测试应该是有用的。
