摘要
乳酸代谢作为肿瘤代谢重编程中的关键环节,在胰腺癌的发生、发展及治疗耐药中发挥重要作用。乳酸不仅是糖酵解的产物,更是调控肿瘤增殖、侵袭、免疫逃逸及药物耐受等生物过程的信号分子。近年来,随着乳酸代谢机制研究的深入,乳酸脱氢酶A(lactate dehydrogenase A,LDHA)和单羧酸转运蛋白(monocarboxylate transporter,MCT)等靶点在胰腺癌中的潜在治疗价值逐渐显现。已有临床前研究显示,靶向乳酸代谢可有效抑制肿瘤生长并改善免疫抑制微环境,乳酸相关生物标志物可辅助胰腺癌的诊断与预后评估。然而,当前乳酸靶向药物仍面临选择性差、安全性和稳定性不足等问题。文章综述了乳酸代谢在胰腺癌中的作用机制、关键靶点及其治疗策略,进一步探讨乳酸干预与免疫治疗等联合方案的研究进展,以期为胰腺癌患者提供更有效的治疗路径和理论参考。
As a key link in tumor metabolic reprogramming,lactate metabolism plays an important role in the occurrence,development and treatment resistance of pancreatic cancer.Beyond being a glycolytic byproduct,lactate functions as a key signaling molecule that regulates tumor proliferation,invasion,immune escape,and drug tolerance.Recent advances have identified lactate dehydrogenase A(LDHA)and monocarboxylate transporters(MCTs)as promising therapeutic targets in pancreatic cancer.Preclinical studies have shown that targeting lactate metabolism can suppress tumor growth and remodel the immunosuppressive tumor microenvironment.Moreover,lactate-associated biomarkers can also assist in the diagnosis and prognosis of pancreatic cancer.Despite these advances,current lactate-targeted therapies are limited by poor specificity,suboptimal safety,and pharmacological instability.This review outlines the mechanistic underpinnings of lactate metabolism in pancreatic cancer,highlights emerging therapeutic targets and strategies,and discusses the potential of integrating lactate-targeted approaches with immunotherapy to improve clinical outcomes.
作者
吴佳懿
朱春富
徐克群
WU Jiayi;ZHU Chunfu;XU Kequn(Department of Oncology,the Third Affiliated Hospital of Nanjing Medical University,Changzhou 213000,China;Department of General Surgery,the Third Affiliated Hospital of Nanjing Medical University,Changzhou 213000,China)
出处
《南京医科大学学报(自然科学版)》
北大核心
2025年第10期1513-1520,共8页
Journal of Nanjing Medical University(Natural Sciences)
基金
常州市医学创新团队项目(CCX201807)。
关键词
乳酸
肿瘤代谢
胰腺癌
靶向治疗
lactate
tumor metabolism
pancreatic cancer
targeted therapy
