非小细胞肺癌表皮生长因子受体酪氨酸激酶抑制剂耐药机制研究进展

以吉非替尼和厄罗替尼为代表的表皮生长因子受体酪氨酸激酶抑制剂在部分非小细胞肺癌患者中的治疗效果显著,但几乎所有患者最终均表现为耐药.因此,为提高该类药物的效用,对耐药性的研究便显得至关重要.基因突变、细胞表型改变、受体内化、信号通路成分及其调节因子的基因表达改变等都可以导致肿瘤细胞摆脱对表皮生长因子受体信号通路的专一性依赖而产生耐药.

Updates on resistance mechanisms of epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancer

Efficacy of epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKI)such as gefitinib and erlotinib is outstanding in the second or third-line treatment of some non-small cell lung cancer patients.However,disease in nearly all patients will aquire resistance to the drugs.Therefore,a better understanding of the mechanisms of resistance to EGFR kinase inhibitor is critical to further improve the efficacy of this class of agents.Genetic mutations of EGFR,cellular phenotypic changes,internalization of EGFR,the constitutive activation of downstream signal molecules or bypass signal pathway activation may provide tumor cells the ability of being independent of EGFR signaling and acquiring resistance tO EGFRTKI.