CAJ | 학술논문

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。
목전，폐암시전세계범위내발병솔화사망솔최고적악성종류，기중비소세포폐암（non-small cell lung cancer, NSCLC）점전부폐암적80%좌우，이NSCLC환자중유흔대일부분재학진시이경처우만기。인차，대우만기NSCLC적치료야월래월수도인문적중시。수연만기NSCLC적표준치료위함박쌍약연합화료，단시화료약물대개선만기NSCLC환자적생존기방면작용십분유한，인차심구신적치료방식박재미첩。수착대폐암발병궤제급기생물학행위적심입연구，분자파향치료이성위치료만기NSCLC최구전경적연구영역。기중표피생장인자수체-락안산격매억제제（epidermal growth factor receptor tyrosine kinase inhibitors, EGFR-TKIs）재만기NSCLC치료방면취득료돌파성진전，기대표약물위길비체니화액락체니，저량충EGFR-TKIs이재전세계범위내득도인가병피엄범용우만기NSCLC적치료，우기시대우EGFR민감돌변자。연이，경과일단시간（중위시간위6개월-12개월）적치료후，대부분환자회대EGFR-TKIs산생내약，기내약궤제주요포괄원발성화획득성내약。유우EGFR-TKIs재개선만기NSCLC환자총생존기화무진전생존기방면적돌출작용，대우EGFR-TKIs내약궤제적탐색이성위국내외연구적열점。해문장취EGFR-TKI내약궤제적연구진전진행료종술。
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.