Prostate cancer (PCa) is the second most common malignancy among men in the world. Castration-resistant prostate cancer (CRPC) is the lethal form of the disease, which develops upon resistance to ifrst line androgen deprivation therapy (ADT). Emerging evidence demonstrates a key role for the PI3K-AKT-mTOR signaling axis in the development and maintenance of CRPC. This pathway, which is deregulated in the majority of advanced PCas, serves as a critical nexus for the integration of growth signals with downstream cellular processes such as protein synthesis, proliferation, survival, metabolism and differentiation, thus providing mechanisms for cancer cells to overcome the stress associated with androgen deprivation. Furthermore, preclinical studies have elucidated a direct connection between the PI3K-AKT-mTOR and androgen receptor (AR) signaling axes, revealing a dynamic interplay between these pathways during the development of ADT resistance. Thus, there is a clear rationale for the continued clinical development of a number of novel inhibitors of the PI3K pathway, which offer the potential of blocking CRPC growth and survival. In this review, we will explore the relevance of the PI3K-AKT-mTOR pathway in PCa progression and castration resistance in order to inform the clinical development of speciifc pathway inhibitors in advanced PCa. In addition, we will highlight current deifciencies in our clinical knowledge, most notably the need for biomarkers that can accurately predict for response to PI3K pathway inhibitors.

去势抵抗性前列腺癌的治疗

去势抵抗性前列腺癌（Castrate-resistant prostate cancer，CRPC）指经过初次持续雄激素剥夺治疗后疾病依然进展的前列腺癌，是晚期前列腺癌病情发展的重要阶段。CRPC患者根据是否存在转移病灶、既往接受治疗以及体力状况等可进一步分类，恰当的药物治疗可使患者获益。本文从诊断、病因、分类、药物选择4个角度对CRPC的治疗进行综述，旨在为临床药师的工作实践提供参考。

AR受体对前列腺癌细胞中IgG蛋白表达的影响

目的:研究雄激素受体(AR)对雄激素依赖型及非依赖型前列腺癌细胞IgG mRNA和蛋白表达的影响.方法:采用AR基因转染前列腺癌PC3细胞得到PC3-AR,培养LNCap细胞的非雄激素依赖亚型C4-2,检测AR表达,IgG mRNA及蛋白表达量.结果:AR在PC3,PC3-V,LNCap细胞中呈低表达,在PC3-AR,C4-2呈高表达.IgG mRNA及蛋白表达量在PC3-AR、LNCaP细胞中呈低表达,在PC3、C4-2细胞中呈高表达.结论:AR表达与前列腺癌细胞恶性程度相关,前列腺癌细胞AR的缺失导致其IgG mRNA及蛋白表达量增加.

前列腺癌细胞株PC-3经Doc处理后p-c-jun和AR的表达变化

目的 探讨多西紫杉醇的细胞毒性化疗反应的分子机制.方法 对体外的免疫印迹、荧光素酶和细胞生存率进行分析,研究PC-3细胞暴露在多西紫杉醇后p-c-jun的过表达与AR的相互作用.结果 多西紫杉醇治疗PC-3细胞敏感,细胞对多烯紫杉醇的敏感性与p-c-jun水平呈负相关.转染c-jun基因转染到PC-3细胞降低了多烯紫杉醇的敏感性,而转染c-jun和AR基因则可以恢复到中等程度敏感性.p-c-jun与AR蛋白水平之间没有发现直接相关性.对多烯紫杉醇的治疗反应,体内模型的结果与体外研究结果是一致的.结论 p-c-jun可能是多西紫杉醇对前列腺癌治疗的分子机制之一.

Si mpuleucel-T疫苗治疗转移去势抵抗性前列腺癌新进展

Sipuleucel‐T是首个被美国FDA批准用于晚期前列腺癌治疗的疫苗制剂，能使中位生存期的延长超过两年。它被美国国立综合癌症网络（NCCN）指南作为Ⅰ级推荐用于无症状或有轻微症状的转移去势抵抗性前列腺癌（mCRPC）患者的治疗。本文旨在系统综述Sipuleucel‐T疫苗治疗mCRPC的机制、方法、临床使用指征、临床试验、循证证据及联合应用等方面的新进展。