Effects of Androgen and Estrogen Receptor Signaling Pathways on Bladder Cancer Initiation and Progression.
Effects of Androgen and Estrogen Receptor Signaling Pathways on Bladder Cancer Initiation and Progression.
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DOI：
10.3233/blc-160052
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发表时间：
2016-04-27
期刊：
影响因子：
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通讯作者：
Fahmy O
中科院分区：
文献类型：
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作者：
Godoy G;Gakis G;Smith CL;Fahmy O
流行病学研究早就证明了膀胱癌的发病率和进展在性别上的明显差异，这表明这些肿瘤的发生和进展机制与类固醇激素通路密切相关。这些观察结果导致临床前研究调查雄激素和雌激素受体的作用，以及它们的同源激素在膀胱癌的发生和发展。通过各种体外细胞系测定和体内小鼠模型，研究已经阐明了这些类固醇受体参与该疾病的不同机制和信号通路。最近，来自多项研究的RNA表达数据显示，膀胱癌的一种腔内亚型表现出雌激素受体信号通路，这使其成为未来进一步考虑靶向治疗的强有力候选者。尽管临床前数据显示，针对这些途径的抗雄激素和抗雌激素策略在膀胱癌的不同阶段具有潜在作用，但目前只有两项临床试验正在进行，并为此类临床研究积累患者。膀胱癌的靶向治疗是一个巨大的未满足的需求，有可能改变治疗模式和改善膀胱癌患者的肿瘤预后。
Epidemiologic studies have long demonstrated clear differences in incidence and progression of bladder cancer between genders suggesting that the mechanisms of development and progression in these tumors have a strong association with steroid hormonal pathways. Such observations led to preclinical studies investigating the role of androgen and estrogen receptors, as well as their cognate hormones in bladder cancer initiation and progression. Using various in vitro cell line assays and in vivo mouse models, studies have elucidated different mechanisms and signaling pathways through which these steroid receptors may participate in this disease. More recently, RNA expression data from multiple studies revealed a luminal subtype of bladder cancer that exhibited an estrogen receptor signaling pathway, making it a strong candidate for further consideration of targeted therapies in the future. Despite the promising preclinical data demonstrating potential roles for both antiandrogen and antiestrogen strategies targeting these pathways in different stages of bladder cancer, only two clinical trials are currently active and accruing patients for such clinical studies. Targeted therapies in bladder cancer are a large unmet need and have the potential to change treatment paradigms and improve oncological outcomes of patients with bladder cancer.