葡萄糖代谢重编程在胰腺癌耐药中的研究进展

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

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。

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.