蛋白降解靶向嵌合体在消化道肿瘤中的应用进展  

Advances in the application of proteolysis targeting chimeras in gastrointestinal tumors

作　　者：雷靖 阮露晞 杨晖 陈美丽 袁忆航 李惠子 张全安 LEI Jing;RUAN Luxi;YANG Hui;CHEN Meili;YUAN Yihang;LI Huizi;ZHANG Quan'an(Department of Oncology,The Affiliated Jiangning Hospital of Nanjing Medical University,Nanjing,Jiangsu 211100,China)

机构地区：[1]南京医科大学附属江宁医院肿瘤科,江苏南京211100

出　　处：《中国临床研究》2024年第3期464-468,共5页Chinese Journal of Clinical Research

基　　金：江苏省自然科学基金项目(BK20161110)。

摘　　要：蛋白降解靶向嵌合体(PROTAC)是一种有效的靶向蛋白降解(TPD)策略。作为一种异源双功能分子,PROTAC由目标蛋白(POI)共轭物、连接器和E3连接酶配体组成,能够通过劫持细胞的泛素—蛋白酶体系统(UPS)来诱导蛋白质的泛素化蛋白酶体降解,从而从细胞中移除特定的致癌蛋白。目前,已有越来越多的靶向消化道肿瘤的PROTAC成功研发,其中许多POI已被证实为有效的临床药物靶点。本文将详细阐述PROTAC的工作机制、研究进展以及其在消化道肿瘤研究中的应用,并将探讨PROTAC在癌症治疗中的优势、潜在挑战以及其在未来抗肿瘤治疗中的前景。Proteolysis targeting chimera(PROTAC) represents an effective strategy for targeted protein degradation(TPD).As a heterobifunctional molecule,PROTAC is composed of a conjugate for the protein of interest(POI),a linker,and an E3 ligase ligand.It induces ubiquitin-proteasome system(UPS)-mediated protein degradation by hijacking the cellular UPS,thereby removing specific oncogenic proteins from cells.Till now,an increasing number of PROTACs targeting gastrointestinal cancer have been successfully developed,with many POIs validated as effective targets for clinical drugs.This article will elucidate the working mechanism of PROTACs,their research progress,and their applications in the study of gastrointestinal cancer.Furthermore,it will explore the advantages and potential challenges of PROTACs in cancer treatment,as well as their prospects in future antitumor therapies.

关 键 词：蛋白降解靶向嵌合体 靶向蛋白质降解 消化道肿瘤 E3连接酶 

分 类 号：R735.2[医药卫生—肿瘤]