胰腺癌细胞内吉西他滨耐药机制的研究进展  

Research advances of intracellular mechanisms underlying gemcitabine resistance in pancreatic cancer

作　　者：顾宗廷 李宗泽 王成锋 Zong-Ting Gu;Zong-Ze Li;Cheng-feng Wang(State Key Lab of Molecular Oncology&Department of Pancreatic and Gastric Surgery,National Cancer Center/Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100021,China)

机构地区：[1]国家癌症中心/国家肿瘤临床医学研究中心/中国医学科学院北京协和医学院肿瘤医院分子肿瘤学国家重点实验室/胰胃外科,北京市100021

出　　处：《世界华人消化杂志》2020年第22期1150-1161,共12页World Chinese Journal of Digestology

基　　金：中国医学科学院医学与健康科技创新工程,No.2016-I2M-1-001.

摘　　要：胰腺癌是人类最具致命的恶性肿瘤之一,其中胰腺导管腺癌(pancreatic ductal adenocarcinoma,PDAC)是最常见的组织学类型.由于PDAC早期缺乏特异的临床症状、体征及有效的筛查标志物,仅15%-20%的患者具备手术切除条件.因此,以吉西他滨(gemcitabine,GEM)为基础的单药或联合化疗仍是目前最主要甚或唯一的治疗方案.然而,PDAC对GEM的总反应率不足20%,对GEM耐药是影响化疗疗效的最重要原因之一.目前GEM耐药的机制并不明确,可能涉及先天性和获得性两个方面,PDAC的异质性则进一步增加了其复杂性.然而,细胞内信号通路调控是实现GEM抵抗的最终途径.本文将重点对GEM在PDAC细胞内的代谢和信号通路调控的研究进展进行综述,讨论潜在的GEM化疗增敏策略,以期提高化疗有效率,改善PDAC的总体预后.Pancreatic cancer is one of the most deadly malignant tumors that endanger human health,and pancreatic ductal adenocarcinoma(PDAC)is the most common histological type.Due to the lack of specific clinical symptoms,physical signs,and effective screening biomarkers for early stage PDAC,only 15%-20%of patients are qualified for surgical resection.Consequently,gemcitabine(GEM)-based monotherapy or combination therapy is still the most important or even the only treatment option.However,the overall response rate of PDAC to GEM is less than 20%,and GEM resistance is one of the most important factors affecting the efficacy of chemotherapy.At present,the mechanism of GEM resistance has not been clarified,which may involve congenital and acquired regulation.The heterogeneity of PDAC further increases its complexity.However,regulation of intracellular signaling pathways is the ultimate event to induce GEM resistance.This article will review the recent advances in research of GEM metabolism and regulation of signaling pathways in PDAC cells,and discuss potential GEM chemosensitization strategies,in order to improve the effective rate of chemotherapy and the outcome.

关 键 词：胰腺癌 胰腺导管腺癌 吉西他滨 代谢 化疗耐药 

分 类 号：R735.9[医药卫生—肿瘤]