肝X受体激动剂对EGFR下游通路的抑制作用

The inhibitory effects of the liver X receptor agonists on the EGFR associated signal pathway

表皮生长因子受体-酪氨酸激酶抑制剂(EGFR-TKI)是目前应用最广泛的肺癌靶向药物,但几乎所有治疗有效的患者最终都会对EGFR-TKI产生继发耐药,耐药机制主要为EGFR下游通路被再度激活。肝X受体(LXR)属于核受体家族,多项研究表明LXR激动剂对EGFR最重要的下游通路PI3K/AKT/NF-κB多个主要环节均有不同程度的抑制作用。因此,LXR激动剂可能是逆转EGFR-TKI继发耐药的新选择。本文主要对近年来LXR激动剂对PI3K/AKT/NF-κB通路的抑制作用进行综述。

Epidermal growth factor receptor tyrosine kinase inhibitor（ EGFR.TKI） is the most widely used drug in the targeted treatment of lung cancer. However, almost all patients who are effective to this drug will eventually develop secondary resistance to EG.FR.TKI. The main mechanism of resistance is that the EGFR associated signal pathway was again activated. The liver X receptor（ LXR） belongs to the family of nuclear receptor. Many studies showed the inhibitory effects of LXR agonists on the signal pathway of PI3K/AKT/NF.κB that are important to EGFR. Therefore, LXR agonists may be a potential new choice that can reverse the secondary resist.ance of EGFR.TKI. This paper summarizes the recent findings about the inhibitory effects of LXR agonists on PI3K/AKT/NF-κB path.way.