EGFR和ALK靶向治疗及其耐药机制的研究进展

Research progress of EGFR and ALK targeted therapy and its drug resistance mechanism

表皮生长因子受体(EGFR)是一种具有酪氨酸激酶活性的受体;棘皮类微管相关样蛋白-4-间变型淋巴瘤激酶(EML4-ALK)是EML4与ALK的融合基因,EGFR突变及EML4-ALK阳性都能促进肿瘤细胞增殖并抑制肿瘤细胞的凋亡。研究发现,在非小细胞肺癌(NSCLC)患者中有大量出现EGFR突变及EML4-ALK阳性,且当前对于该类患者EGFR和ALK抑制剂是首选治疗方式。但此治疗方式易出现耐药而限制其作用效果,因此探寻其耐药机制及耐药后治疗的新策略显得尤为重要。目前关于NSCLC耐药机制的研究已经逐步展开,并且逆转NSCLC患者获得性耐药的治疗策略也已有了初步的成效。本综述旨在总结EGFR突变和ALK阳性的NSCLC患者获得性耐药机制的新进展和克服耐药的新策略。

Epidermal growth factor receptor（EGFR） is a receptor with tyrosine kinase activity; echinoderm microtubule-associated protein like 4-anaplastic lymphoma kinase（EML4-ALK） is a fusion gene with EML4 and ALK, and they both play a vital role in promoting proliferation and inhibiting apoptosis in tumor cells. Research finds that in non-small cell lung cancer（NSCLC） patients, many have EGFR mutate and ALK-positive, and currently, EGFR and ALK inhibitor is the preferred treatment for this kind of patients. However, this treatment makes patients prone to drug resistance and limit its effect. Thus, it is really important to find the mechanisms and explore new strategies for drug resistance. At present, the research on the drug resistance mechanism of NSCLC has been gradually expanded, and the treatment strategy for reversal of NSCLC patients with acquired resistance has preliminary effects. This review tends to summarize advanced developments of acquired drug resistance in NSCLC, taking on EGFR mutation and rearrangement of ALK, and new strategies to overcome resistance.