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

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。

The mechanism of androgen independent signaling pathway in castration-resistant prostate cancer and the research progress on related drugs

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.