EGFR-TKI在非小细胞肺癌中耐药机制的研究进展

Research Progress of the Resistance Mechanism of Non-small Cell Lung Cancer to EGFR-TKIs

目前,肺癌是全世界范围内发病率和死亡率最高的恶性肿瘤,其中非小细胞肺癌(non-small cell lung cancer,NSCLC)占全部肺癌的80%左右,而NSCLC患者中有很大一部分在确诊时已经处于晚期。因此,对于晚期NSCLC的治疗也越来越受到人们的重视。虽然晚期NSCLC的标准治疗为含铂双药联合化疗,但是化疗药物对改善晚期NSCLC患者的生存期方面作用十分有限,因此寻求新的治疗方式迫在眉睫。随着对肺癌发病机制及其生物学行为的深入研究,分子靶向治疗已成为治疗晚期NSCLC最具前景的研究领域。其中表皮生长因子受体-酪氨酸激酶抑制剂(epidermal growth factor receptor tyrosine kinase inhibitors,EGFR-TKIs)在晚期NSCLC治疗方面取得了突破性进展,其代表药物为吉非替尼和厄洛替尼,这两种EGFR-TKIs已在全世界范围内得到认可并被广泛用于晚期NSCLC的治疗,尤其是对于EGFR敏感突变者。然而,经过一段时间(中位时间为6个月-12个月)的治疗后,大部分患者会对EGFR-TKIs产生耐药,其耐药机制主要包括原发性和获得性耐药。由于EGFR-TKIs在改善晚期NSCLC患者总生存期和无进展生存期方面的突出作用,对于EGFR-TKIs耐药机制的探索已成为国内外研究的热点。该文章就EGFR-TKI耐药机制的研究进展进行了综述。

Nowadays, lung cancer is the malignant tumor of the highest morbidity and mortality over the world, and non-small cell lung cancer （NSCLC） makes up about 80%. hTere is a great many NSCLC patients have been in advanced stage when diagnosed. As a result, people pay more attention to curing advanced NSCLC. hTe standard treatment to advanced NSCLC is platinum-based combined chemotherapy. However, chemotherapy drugs usually have limited effects on improving the survival of the patients. hTen exploring new therapies is extremely urgent to us. Now, molecular targeted therapy has been the most promising research area for the treatment of NSCLC with researches going deep into pathogenesis and biological behavior of lung cancer. Epidermal growth factor receptor-tyrosine kinase inhibitors （EGFR-TKIs） have achieved a great suc-cess in the treatment of advanced NSCLC. hTeir representatives are erlotinib and geiftinib. hTe two drugs have been widely used to treat advanced NSCLCs worldwide, especially for the patients with EGFR activating mutations. However, atfer a period of treatment （median time is 6 to 12 months）, most patients will develop drug resistance to EGFR-TKIs. Intense research in these NSCLCs has identiifed two major mechanisms of resistance to TKIs：primary and acquired resistances. hTe research about resistance mechanism of NSCLC to EGFR-TKIs is a hot one because of their excellent effects on improving overall and progression-free survival. hTe aim of this article was to summarize the development of the resistance mechanisms.