代谢重编程在非小细胞肺癌表皮生长因子受体酪氨酸激酶抑制剂耐药中的作用

Role of metabolic reprogramming in drug resistance to epidermal growth factor tyrosine kinase inhibitors in non-small cell lung cancer

表皮生长因子受体酪氨酸激酶抑制剂(epidermal growth factor receptor tyrosine kinase inhibitor,EGFRTKI)能够有效地抑制EGFR基因突变驱动型非小细胞肺癌(non-small cell lung cancer,NSCLC)的生长,但NSCLC患者在经过长时间持续的EGFR-TKI治疗后往往会发生严重的耐药。研究表明肿瘤细胞能量代谢紊乱对EGFR-TKI耐药的产生具有重要的诱导作用。在药物、基因突变等多种因素的作用下肿瘤细胞会发生代谢重编程,上调肿瘤细胞的代谢速率和强度,促进肿瘤对糖、脂肪、谷氨酰胺等营养物质的摄入和利用,并形成有利于肿瘤生长的微环境,促进肿瘤细胞的旁路激活、表型转化、异常增殖等,从而抑制免疫细胞的活性和肿瘤细胞的凋亡,导致肿瘤细胞对EGFR-TKI产生耐药性。

Epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKI)can effectively inhibit the growth of EGFR-dependent mutant non-small cell lung cancer(NSCLC).Unfortunately,NSCLC patients often develop severe drug resistance after long-term EGFR-TKI treatment.Studies have shown that the disorder of energy metabolism in tumor cells can induce EGFR-TKI resistance.Due to the drug action,gene mutation and other factors,tumor cells undergo metabolic reprogramming,which increases the metabolic rate and intensity of tumor cells,promotes the intake and synthesis of nutrients(such as sugar,fat and glutamine),forms a microenvironment conducive to tumor growth,enhances the bypass activation,phenotype transformation and abnormal proliferation of tumor cells,and inhibits the activity of immune cells and apoptosis of tumor cells,ultimately leading to drug resistance of tumor cells to EGFR-TKI.Therefore,targeting energy metabolism of NSCLC may be a potential way to alleviate TKI resistance.