Keap1/Nrf2/ARE信号通路介导非小细胞肺癌耐药机制的研究进展

Research progress on Keap1/Nrf2/ARE signaling pathways mediating the drug resistance mechanisms in non-small cell lung cancer

近十年来,非小细胞肺癌基础及其转化性研究,从癌细胞驱动基因筛选及其靶向干预方面的研究,到肿瘤细胞微环境研究,正逐渐改变传统理念,也成为非小细胞肺癌研究最活跃的领域。组织缺氧与抗氧化系统是影响肿瘤微环境、改变肿瘤细胞药物敏感性的重要机制之一。Keap1/Nrf2/ARE信号转导通路是机体最重要的抗氧化应激系统之一。近年来,越来越多研究表明,Keap1/Nrf2/ARE信号通路与肿瘤细胞耐药有着密切的关系,调控该通路关键激酶磷酸化过程有望成为新的耐药干预靶点。

In recent ten years,the fundamental research and translational rasearch of non small cell lung cancer is witnessing a change on traditional theory,from the research on cancer cell driver gene selection and its relevant target interference to the rasearch on tumor microenvironment. It has become the most active research area in NSCLC. Hy-poxia and antioxidant system is one of the important influence mechanisms affecting the tumor microenvironment and changing the drug sensitivity for tumor cell. Keap/ Nrf2 / ARE signal pathway is one of the most important antioxidant tress systems in organism. More and more research in recent years show that there exists a close relationship between Keap / Nrf2 / ARE signaling pathway and tumor cells drug resistance. It can be foreseen that regulating the phosphoryla-tion of key kinase in such pathway will be a new target in drug - resistance.