药学学报, 2021, 56(1): 21-28
引用本文:
薛梦侠, 古悦, 孙建国, 王广基, 彭英. 去势抵抗前列腺癌中的非激素信号通路作用机制及其相关药物研究进展[J]. 药学学报, 2021, 56(1): 21-28.
XUE Meng-xia, GU Yue, SUN Jian-guo, WANG Guang-ji, PENG Ying. The mechanism of androgen independent signaling pathway in castration-resistant prostate cancer and the research progress on related drugs[J]. Acta Pharmaceutica Sinica, 2021, 56(1): 21-28.

去势抵抗前列腺癌中的非激素信号通路作用机制及其相关药物研究进展
薛梦侠, 古悦, 孙建国, 王广基, 彭英
中国药科大学药物代谢动力学重点实验室, 江苏 南京 210009
摘要:
前列腺癌是男性泌尿生殖系统常见的恶性肿瘤之一,近十年来我国前列腺癌的发病率呈明显上升的趋势。目前,以雄激素阻断为主的内分泌治疗是除根治手术和放疗或化疗之外临床上比较主流的前列腺癌治疗方案,虽然在治疗前期能获得良好的临床收益,但近九成的患者仍会进入去势抵抗阶段,且其中又有近九成的患者会发生骨转移,患者的生活质量随着疾病进程急剧降低。有研究表明在形成去势抵抗的过程中,除雄激素信号通路外还涉及了多种其他分子信号的变化,包括经典的致癌信号通路和免疫炎症致癌信号通路等。了解这些独立于雄激素信号通路的其他信号通路在去势抵抗形成中的作用机制,将有助于了解雄激素阻断治疗在去势抵抗中的脱靶效应以及引入新的治疗靶点和治疗策略,推动去势抵抗摆脱临床“无药可用”的困境。
关键词:    前列腺癌      去势抵抗      非雄激素依赖      信号通路      药物研发     
The mechanism of androgen independent signaling pathway in castration-resistant prostate cancer and the research progress on related drugs
XUE Meng-xia, GU Yue, SUN Jian-guo, WANG Guang-ji, PENG Ying
Key Lab of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China
Abstract:
Prostate cancer is one of the common malignant tumors of male urogenital system, and the incidence of prostate cancer in China has increased significantly in the past decade. At present, endocrine therapy based on androgen blockade is the main method of clinical treatment except radical surgery and radiotherapy/chemotherapy for prostate cancer. However, the clinical benefit can only be obtained in the early stage of treatment, and nearly 90% of patients will develop to the castration resistance, and among them, nearly 90% of patients will have bone metastasis. The quality of life decreases sharply with the progression of disease for patients. In addition to the androgen signal pathway, studies have shown that many other oncogenic signal pathways have involved in the development of castration resistance, including classic cancer signaling pathways, immune and inflammatory signaling pathways, etc. Understanding the mechanism of androgen independent signal pathway in the formation of castration resistance will help to understand the off-target effect of androgen blocking therapy and introduce new treatment targets or strategies to get rid of the "no drug available" dilemma for clinical treatment of castration resistance.
Key words:    prostate cancer    castration resistance    androgen independent    signal pathway    drug development   
收稿日期: 2020-07-13
DOI: 10.16438/j.0513-4870.2020-1162
基金项目: 国家自然科学基金资助项目(81703608);江苏省自然科学基金资助项目(BK20170741).
通讯作者: 王广基,Tel:86-25-83271176,E-mail:guangjiwang@hotmail.com;彭英,Tel:13770828062,E-mail:pengy2014@126.com
Email: guangjiwang@hotmail.com;pengy2014@126.com
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