鼻咽癌代谢重编程与放疗抵抗

Metabolic reprogramming in regulating radiotherapy resistance of nasopharyngeal carcinoma

鼻咽癌是一种具有地域分布性的鼻咽上皮恶性肿瘤,放疗抵抗是鼻咽癌患者治疗失败的主要原因。代谢重编程是调控肿瘤发生发展的核心,代谢变化能够影响肿瘤的发生、发展及治疗抵抗。糖酵解、氧化磷酸化、脂肪酸氧化等代谢途径均参与肿瘤放疗敏感性的调控。肿瘤微环境变化、基因突变或基因异常表达、基因表观遗传修饰或某些信号通路异常激活是调控鼻咽癌放疗抵抗的主要机制。近年来,越来越多的研究显示,代谢重编程在鼻咽癌放疗抵抗中扮演了重要角色,可通过调控DNA损伤修复、细胞周期、凋亡与自噬、肿瘤细胞干性和免疫反应等来调节鼻咽癌细胞的放疗抗性。靶向代谢重编程可为鼻咽癌放疗增敏提供新的策略和思路。

Nasopharyngeal carcinoma(NPC)is a kind of nasopharyngeal epithelial malignant tumor with regional distribution.Radiotherapy resistance has become the main cause of treatment failure in patients with nasopharyngeal carcinoma.The core of the regulation of the occurrence and development of tumor lies in metabolic reprogramming,since metabolic changes can affect the occurrence,development and treatment resistance of tumor.Metabolic pathways such as glycolysis,oxidative phosphorylation,and fatty acid oxidation are involved in the regulation of tumor radiosensitivity.Changes of tumor microenvironment,gene mutation or abnormal gene expression,gene epigenetic modification or abnormal activation of some signal pathways are the main mechanisms that regulate the radiotherapy resistance of NPC.In recent years,a growing number of studies have shown that metabolic reprogramming plays a very important role in radiotherapy resistance of NPC.The radiotherapy resistance of NPC cells can be adjusted by regulating DNA damage repair,cell cycle,apoptosis and autophagy,tumor cell stemness and immune response.Targeting metabolic reprogramming can provide new strategies and ideas for NPC radiosensitization.