Mao Hai-Lei, Zhu Zhi-Qi, Chen Charlie Degui
State Key Laboratory of Molecular Biology, Shanghai Key Laboratory of Andrology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Asian J Androl. 2009 Jan;11(1):69-73. doi: 10.1038/aja.2008.14. Epub 2008 Dec 1.
Advanced prostate cancer is responsive to hormone therapy that interferes with androgen receptor (AR) signalling. However, the effect is short-lived, as nearly all tumours progress to a hormone-refractory (HR) state, a lethal stage of the disease. Intuitively, the AR should not be involved because hormone therapy that blocks or reduces AR activity is not effective in treating HR tumours. However, there is still a consensus that AR plays an essential role in HR prostate cancer (HRPC) because AR signalling is still functional in HR tumours. AR signalling can be activated in HR tumours through several mechanisms. First, activation of intracellular signal transduction pathways can sensitize the AR to castrate levels of androgens. Also, mutations in the AR can change AR ligand specificity, thereby allowing it to be activated by non-steroids or anti-androgens. Finally, overexpression of the wild-type AR sensitizes itself to low concentrations of androgens. Therefore, drugs targeting AR signalling could still be effective in treating HRPC.
晚期前列腺癌对干扰雄激素受体（AR）信号传导的激素疗法有反应。然而，这种效果是短暂的，因为几乎所有肿瘤都会进展到激素难治性（HR）状态，这是该疾病的一个致命阶段。直观地说，AR不应参与其中，因为阻断或降低AR活性的激素疗法对治疗HR肿瘤无效。然而，仍有一个共识，即AR在HR前列腺癌（HRPC）中起重要作用，因为AR信号传导在HR肿瘤中仍然发挥作用。AR信号传导可以通过几种机制在HR肿瘤中被激活。首先，细胞内信号转导途径的激活可以使AR对去势水平的雄激素敏感。此外，AR中的突变可以改变AR配体特异性，从而使其被非甾体类或抗雄激素激活。最后，野生型AR的过表达使其自身对低浓度雄激素敏感。因此，靶向AR信号传导的药物仍可能对治疗HRPC有效。
