Mizushima Taichi, Tirador Kathleen A, Miyamoto Hiroshi
a Department of Pathology and Laboratory Medicine , University of Rochester Medical Center , Rochester , NY , USA.
b Wilmot Cancer Institute , University of Rochester Medical Center , Rochester , NY , USA.
Expert Opin Ther Targets. 2017 Mar;21(3):249-257. doi: 10.1080/14728222.2017.1280468. Epub 2017 Jan 19.
Patients with non-muscle-invasive or muscle-invasive bladder cancer undergoing surgery and currently available conventional therapy remain having a high risk of tumor recurrence or progression, respectively. Novel targeted molecular therapy is therefore expected to improve patient outcomes. Meanwhile, substantially higher incidence of bladder cancer in men has prompted research on androgen-mediated androgen receptor (AR) signaling in this malignancy. Indeed, preclinical evidence has suggested that AR signaling plays an important role in urothelial carcinogenesis and tumor outgrowth as well as resistance to some of the currently available conventional non-surgical therapies. Areas covered: We summarize and discuss available data suggesting the involvement of AR and its potential downstream targets in the development and progression of bladder cancer. Associations between AR signaling and sensitivity to cisplatin/doxorubicin or bacillus Calmette-Guérin treatment are also reviewed. Expert opinion: AR activation is likely to correlate with the promotion of urothelial carcinogenesis and cancer outgrowth as well as resistance to conventional therapies. Molecular therapy targeting the AR may thus provide effective chemopreventive and therapeutic approaches for urothelial cancer. Accordingly, bladder cancer can now be considered as an endocrine-related neoplasm. Clinical application of various anti-AR therapies available for AR-dependent prostate cancer to bladder cancer patients is anticipated.
接受手术及现有传统治疗的非肌层浸润性或肌层浸润性膀胱癌患者，分别仍有较高的肿瘤复发或进展风险。因此，新型靶向分子疗法有望改善患者预后。与此同时，男性膀胱癌发病率显著更高，促使人们对雄激素介导的雄激素受体（AR）信号传导在这种恶性肿瘤中的作用展开研究。确实，临床前证据表明，AR信号传导在尿路上皮癌发生、肿瘤生长以及对一些现有传统非手术治疗的耐药性方面发挥着重要作用。涵盖领域：我们总结并讨论现有数据，这些数据表明AR及其潜在下游靶点参与了膀胱癌的发生和进展。还综述了AR信号传导与对顺铂/阿霉素或卡介苗治疗敏感性之间的关联。专家观点：AR激活可能与尿路上皮癌发生、癌症生长的促进以及对传统治疗的耐药性相关。因此，针对AR的分子疗法可能为尿路上皮癌提供有效的化学预防和治疗方法。相应地，现在可以将膀胱癌视为一种与内分泌相关的肿瘤。预计可将用于AR依赖性前列腺癌的各种抗AR疗法临床应用于膀胱癌患者。
