胰腺癌肿瘤微环境对吉西他滨耐药性产生的机制和靶向策略  

The Mechanism of Tumor Microenvironment in Gemcitabine Resistance of Pancreatic Cancer and Targeting Strategies

作　　者：贾泽森 王莉 刘志强 JIA Ze-Sen;WANG Li;LIU Zhi-Qiang(National Clinical Research Center of Cancer,Tianjin Key Laboratory of Cancer Prevention and Therapy,Tianjin’s Clinical Research Center of Cancer,Tianjin Medical University Cancer Institute and Hospital,Tianjin Medical Univerisity,Tianjin 300060,China;Shandong Provincial Key Laboratory of Precision Oncology,Shandong Cancer Hospital and Institute,Shandong First Medical University and Shandong Academy of Medical Sciences,Jinan 250022,Shandong,China)

机构地区：[1]国家恶性肿瘤临床医学研究中心,天津市肿瘤防治重点实验室,天津市恶性肿瘤临床研究中心,天津医科大学肿瘤医院,天津300060 [2]山东省精准肿瘤重点实验室,山东省肿瘤医院,山东省山东第一医科大学,济南250022

出　　处：《中国生物化学与分子生物学报》2024年第9期1215-1221,共7页Chinese Journal of Biochemistry and Molecular Biology

基　　金：国家自然科学基金项目(No.82070221,82370209)资助。

摘　　要：胰腺导管腺癌(pancreatic ductal adenocarcinoma,PDAC)是世界范围内因癌症死亡的主要原因之一,目前临床上缺乏对PDAC有效的筛查和治疗手段。近十年来,吉西他滨(gemcitabine)一直被用作治疗PDAC的一线化疗药物,但由于肿瘤耐药性等因素的存在,吉西他滨方案仅能非常有限的改善PDAC患者的总生存期。高度纤维化、缺氧和免疫抑制性的肿瘤微环境的形成是导致PDAC对吉西他滨产生耐药性的重要原因,也是未来克服其耐药性的重要研究方向。本综述回顾了肿瘤微环境对PDAC耐药性产生机制的研究进展,并对未来可能运用于重塑PDAC肿瘤微环境的新技术和潜在靶点做出展望。Pancreatic ductal adenocarcinoma(PDAC)is one of the leading causes of cancer-related mortality worldwide,but current clinical methods lack effective screening and treatment options.Despite the widespread use of gemcitabine as a first-line chemotherapeutic agent in the treatment of PDAC over the past decade,its efficacy is limited by the development of drug resistance,which significantly shortens patient survival.This review systematically elucidates the critical role of the tumor microenvironment in the development of gemcitabine resistance of PDAC cells,highlighting the contributions of the extracellular matrix barrier,hypoxia-induced adaptive changes in cancer cells,and the formation of an immunosuppressive microenvironment as key factors in gemcitabine resistance.Additionally,we also introduce novel strategies for reversing chemoresistance,including advanced drug delivery systems,and provide a comprehensive overview of the current opportunities and challenges.

关 键 词：胰腺导管腺癌 吉西他滨 肿瘤耐药性 肿瘤微环境 

分 类 号：Q291[生物学—细胞生物学]