EGFR-TKIs在非小细胞肺癌中的作用及研究进展

The Role and Research Progress of EGFR-TKIs in Non-small Cell Lung Cancer

肺癌是发病率和死亡率最高的恶性肿瘤,分为非小细胞肺癌(NSCLC)和小细胞肺癌(SCLC)。随着精准医疗的发展,分子靶向治疗在肿瘤领域得到了快速发展和广泛应用,尤其是在非小细胞肺癌中。表皮生长因子受体(EGFR)是NSCLC治疗中公认的有效靶点,靶向EGFR的小分子激酶抑制剂可阻断EGFR细胞内自磷酸化及下游活性信号,又称EGFR-酪氨酸激酶抑制剂(EGFR-TKIs)。近年来,EGFR-TKIs靶向EGFR治疗取得了理想的临床疗效,然而由于肿瘤的异质性和基因组的不稳定性,继发性基因突变、替代信号通路的激活等继发性耐药的广泛出现大大降低了非小细胞肺癌的治愈率,与之对应的耐药问题也不断出现。在本篇综述中,作者总结了前三代EGFR-TKIs在NSCLC中的应用及临床耐药现状,并进一步探讨第四代EGFR-TKIs的研究进展,为NSCLC患者的临床用药提供参考。

Lung cancer is one of the most common malignant tumors in the world, which is divided into non-small-cell lung cancer(NSCLC) and small-cell lung cancer(SCLC).With the development of precision medicine, molecular targeted therapy has been rapidly developed and widely used in cancer, especially in NSCLC.Epidermal growth factor receptor(EGFR) is a recognized effective target in NSCLC treatment.EGFR is the first typical member of the RTK family to be identified, EGFR transmit cellular responses mediating a variety of cellular activities such as cell proliferation, differentiation, cell survival and growth.Small molecule kinase inhibitors target the tyrosine protein kinase activity of EGFR,blocking its intracellular autophosphorylation process and downstream activity signals, also known as EGFR-tyrosine kinase inhibitors(EGFR-TKI).In recent years, EGFR-TKIs targeting EGFR therapy have achieved desirable clinical efficacy;However, due to tumor heterogeneity and genomic instability, the widespread emergence of drug resistance such as gene mutations and activation of alternative signaling pathways has greatly reduced the cure rate of NSCLC,and the corresponding drug resistance problems have continued to emerge.In this review, the application and clinical resistance status of the first three generations of EGFR-TKIs in NSCLC were summarized, and the research progress of the fourth generation EGFR-TKIs were discussed, which could provide reference for the clinical use of NSCLC patients.