Page 86 - 南京医科大学自然版

南京医科大学学报（自然科学版） 第44卷第4期
·524 · Journal of Nanjing Medical University（Natural Sciences） 2024年4月

·综 述·

葡萄糖代谢重编程在胰腺癌耐药中的研究进展

喻 悦，王瑜亮，张 晓 *
南京医科大学国家卫健委抗体技术重点实验室，江苏省抗体药物工程研究中心，江苏 南京 211166

［摘 要］ 胰腺癌是严重危害人类健康的消化道恶性肿瘤，预后差，生存率低。目前临床治疗的药物主要是吉西他滨，但随着
其耐药性的出现，疗效显著降低。肿瘤代谢重编程是肿瘤细胞为满足能量和生物原料的需求，出现了代谢途径调整和改变的
现象。有氧糖酵解异常增强是胰腺癌细胞糖代谢重编程的特征之一，在葡萄糖转运体蛋白和糖酵解关键酶的作用下，通过不
同的信号通路调控化疗耐药。文章对胰腺癌耐药和葡萄糖代谢重编程之间的相关性进行探讨，总结分析其调控机制及信号通
路，并归纳靶向肿瘤细胞有氧糖酵解代谢通路的临床前试验和药物开发情况。
［关键词］ 胰腺癌；葡萄糖代谢重编程；有氧糖酵解；化疗耐药
［中图分类号］ R736.7 ［文献标志码］ A ［文章编号］ 1007⁃4368（2024）04⁃524⁃13
doi：10.7655/NYDXBNS20231154

Research progress of glucose metabolic reprogramming in drug resistance of pancreatic
cancer

YU Yue，WANG Yuliang，ZHANG Xiao *
National Health Commission Key Laboratory of Antibody Techniques，Nanjing Medical University，Jiangsu Province
Engineering Research Center of Antibody Drug，Nanjing 211166，China

［Abstract］ Pancreatic cancer is a highly lethal and aggressive tumor that affects the digestive tract，leading to poor prognosis and low
survival rate. At present，gemcitabine⁃based chemotherapy is widely used in the clinical treatment of pancreatic cancer. However，the
efficacy of chemotherapy has significantly decreased with the emergence of clinical drug resistance. In order to meet its demand of
energy and biological materials，tumors always change its metabolic pathway，which is called tumor metabolic reprogramming. The
abnormal enhancement of aerobic glycolysis is one of characteristics of glucose metabolic reprogramming in pancreatic cancer cells.
The glucose transporter proteins and key enzymes are participated in the processes and regulated chemotherapy resistance through
different signal pathways. The purpose of this study is to summarize the relationship between drug resistance and glucose metabolic
reprogramming in pancreatic cancer. The mechanisms and regulatory signaling pathways are also analyzed. Furthermore，the pre⁃clinical
trials and drug development targeting the glycolysis metabolic pathways are summarized and analyzed.
［Key words］ pancreatic cancer；glucose metabolic reprogramming；aerobic glycolysis；chemotherapy resistance
［J Nanjing Med Univ，2024，44（04）：524⁃535，572］

胰腺癌是严重危害人类健康的消化道恶性肿 肿瘤的第7位，居女性恶性肿瘤的第 11位。目前广
瘤之一，有“万癌之王”之称，预后差，病死率与发病 泛应用于胰腺癌临床化疗的药物主要有吉西他滨、
率比为 0.98，5 年生存率低于 11%。全球范围内，胰 5⁃氟尿嘧啶（5⁃fluorouracil，5⁃Fu）和奥沙利铂等，多
腺癌约占癌症致死原因的 8%，是引起癌症相关死 为DNA合成抑制剂。随着其临床耐药性的出现，化
［1］
亡的第4大肿瘤 。胰腺癌发病率居我国男性恶性 疗疗效显著降低 ［2-4］ 。引起耐药的因素有很多，常见
的有细胞内酶系统异常、转运蛋白的异常表达、细

［基金项目］ 国家自然科学基金（81872426） 胞抗凋亡作用增强、DNA 损伤修复能力增加等 ［5-7］ 。
∗ 近年来，新的耐药机制也被大量报道，因此，探究其
通信作者（Corresponding author），E⁃mail：zhangxiao@njmu.edu.cn