嵌合分子(DHT-PROTAC)在前列腺癌研究中的进展  

The Application and Progress of Chimeric Molecules(DHT-PROTAC) in Prostate Cancer

作　　者：魏海彬[1] 王悦童 孙丰[1] 邵怡[1] 卓见[1] 庞昆[1] 孙晓文[1] 

机构地区：[1]上海交通大学附属第一人民医院泌尿外科,上海200080

出　　处：《现代生物医学进展》2014年第3期590-592,共3页Progress in Modern Biomedicine

基　　金：国家自然科学基金青年基金项目(30600618)

摘　　要：前列腺癌多发于老年男性,已成为老年男性常见肿瘤之一。内分泌治疗目前是晚期前列腺癌主要治疗方法,但仍避免不了前列腺癌最终进展成激素非依赖性前列腺癌,导致内分泌治疗的失败。当前,对前列腺癌细胞株的AR表达的研究,主要集中在DNA水平及mRNA水平,而对AR蛋白翻译后调控的研究较少。近些年来,嵌合分子(DHT-PROTAC)是基于蛋白水平,调控AR蛋白的表达,成为研究前列腺癌转归新的热点。DHT-PROTAC是一种新型人工合成的异型双功能小分子;这种小分子是DHT与泛素连接酶E3识别基团的嵌合体,它不仅能与AR结合,而且能在结合后,诱导AR的泛素化,从而通过泛素-蛋白酶途径降解AR;本文介绍了嵌合分子的作用原理,回顾了近些年前列腺癌的治疗进展,分析了嵌合分子将来在前列腺癌治疗中的应用前景。： Prostate cancer occurs mainly in older men, and has become one of common tumors in older men.Endocrine therapy is the main treatment of advanced prostate cancer, but still can＇t avoid eventually into androgen-independent prostate cancer, leading to the failure of endocrine therapy. At present, AR expression studies of prostate cancer, mainly concentrat in DNA level and mRNA level, while few studies focus on the AR protein post-translational regulation. In recent years, chimeric molecule is based on the protein level, regulating AR protein expression,and become the new hot spot of prostate cancer study. Post-translational degradation of protein plays an important role in cell apoptosis. Chimeric molecule （dihydrotestosterone-based proteolysis-targeting chimeric molecule [DHT-PROTAC]） is a novel synthetic heterobifunctional small molecule; DHT-PROTAC is a chimera of a ligand for Androgen Receptor （AR）, a linker moiety and a ligand for an E3 ubiquitin ligase; DHT-PROTAC induces interaction between the target protein AR and the E3 ubiquitin ligase, leading to artificial polyubiquitination of AR and subsequently degradation via the ubiquitin -proteasome pathway （UPP）. This article focuses the role of the chimeric molecules, investigating the role of AR in cell proliferation and viability in prostate cancer cells,reviewing progress in the treatment of prostate cancer recently, and analysis the application prospects of chimeric molecules in prostate cancer.

关 键 词：嵌合分子 DHT—PROTAC 前列腺癌 进展 

分 类 号：R737.25[医药卫生—肿瘤]