同谋：前列腺癌中 AR 活性和雄激素合成的去调控。
Partners in crime: deregulation of AR activity and androgen synthesis in prostate cancer.
机构信息
Kimmel Cancer Center, Department of Cancer Biology and Department of Urology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
出版信息
Trends Endocrinol Metab. 2010 May;21(5):315-24. doi: 10.1016/j.tem.2010.01.002. Epub 2010 Feb 6.
Abstract
Prostate cancer remains a leading cause of cancer death, as there are no durable means to treat advanced disease. Treatment of non-organ-confined prostate cancer hinges on its androgen dependence. First-line therapeutic strategies suppress androgen receptor (AR) activity, via androgen ablation and direct AR antagonists, whereas initially effective, incurable, 'castration-resistant' tumors arise as a result of resurgent AR activity. Alterations of AR and/or associated regulatory networks are known to restore receptor activity and support resultant therapy-resistant tumor progression. However, recent evidence also reveals an unexpected contribution of the AR ligand, indicating that alterations in pathways controlling androgen synthesis support castration-resistant AR activity. In this report, the mechanisms underlying the lethal pairing of AR deregulation and aberrant androgen synthesis in prostate cancer progression will be discussed.
摘要
前列腺癌仍然是癌症死亡的主要原因，因为目前尚无持久的方法来治疗晚期疾病。非器官受限型前列腺癌的治疗取决于其雄激素依赖性。一线治疗策略通过雄激素剥夺和直接 AR 拮抗剂抑制 AR 活性，虽然最初有效，但不可治愈的“去势抵抗性”肿瘤会因 AR 活性重新出现而产生。已知 AR 和/或相关调节网络的改变可恢复受体活性并支持由此产生的治疗耐药肿瘤进展。然而，最近的证据也揭示了 AR 配体的意外贡献，表明控制雄激素合成的途径改变支持去势抵抗性 AR 活性。在本报告中，将讨论前列腺癌进展中 AR 失调和异常雄激素合成致命配对的机制。
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