三代后的新一代EGFR-TKIs研究进展

Research Progress of New Generation EGFR-TKIs after Third-generation

肺癌是全球死亡率最高的癌种。第一、二代表皮生长因子受体酪氨酸激酶抑制剂(epidermal growth factor receptor-tyrosine kinase inhibitors,EGFR-TKIs)的出现,在一定程度上极大地提高了非小细胞肺癌(non-small cell lung cancer,NSCLC)患者的生存期及生活质量,但大多数患者在经过一段时间的无进展生存期后会产生耐药性,其中以T790M突变为主要耐药机制。针对此耐药突变出现的是以奥希替尼为代表的第三代EGFR-TKIs,其效果显著,然而仍不可避免的出现耐药性,如:C797S突变、间质表皮转化(mesenchymal-epithelial transition,MET)、RAS突变、BRAF突变、小细胞肺癌(small cell lung cancer,SCLC)转化、上皮间质细胞转化(epithelial mesenchymal transition,EMT)等。但是目前第三代EGFR-TKIs耐药后并没有标准有效的治疗方案。故本文主要阐述三代后的新一代EGFRTKIs的研究进展,为后续的研究及治疗提供一定的参考。

Lung cancer has the highest mortality rate in the world.The first-and second-generation epidermal growth factor receptor-tyrosine kinase inhibitors(EGFR-TKIs)greatly improve the survival time and quality of life of patients with non-small cell lung cancer(NSCLC)to some extent.However,after a period of progression-free survival,most patients develop drug resistance,in which T790 M mutation is the mainly resistance mechanism.The third-generation EGFR-TKIs,represented by osimertinib,are found to have significant effect on this resistance.The effect is remarkable,but drug resistance is still inevitable.For example,C797 S mutation,mesenchymal-epithelial transition(MET),RAS mutation,BRAF mutation,transformation of small cell lung cancer(SCLC),transformation of epithelial mesenchymal transition(EMT),etc.But,there is no standard and effective treatment after the third-generation EGFR-TKIs resistance.In this view,we summarize the research progress in the new generation EGFR-TKIs after third-generation,in order to provide some reference for the follow-up research and treatment.