论文部分内容阅读
肺癌的高发病率和高病死率,以及化疗对晚期肺癌疗效的十分有限,使之成为世界性医学难题。最近发现,表皮生长因子受体(epidermal growth factor receptor,EGFR)酪氨酸激酶抑制剂(tyrosine kinases inhibitors,TKIs)的分子靶向治疗可以使晚期非小细胞肺癌瘤体缩小;然而,以Gefitinib和Erlotinib为代表的TKIs治疗敏感性与EGFR基因突变显著相关。研究证实,EGFR最常见发生的19区缺失突变和21区点突变导致相应氨基酸序列和EGFR结构的改变,是其增加药物敏感性的主要机制。此外,EGFR基因扩增和CA重复序列的多态性、EGFR通路下游信号(如p-AKT等)激活、HER2和(或)HER3表达的增加、K-RAS基因突变等因素皆影响其对TKIs的治疗敏感性。鉴于此,进一步研究EGFR基因不同突变的功能,寻找能预测TKIs治疗敏感性的因素,并作为TKIs敏感患者的筛选指标,对于提高晚期肺癌患者TKIs靶向治疗疗效具有重要意义。
High incidence of lung cancer and high mortality, as well as the efficacy of chemotherapy for advanced lung cancer is very limited, making it a worldwide medical problem. Recently, molecular targeted therapy of epidermal growth factor receptor (EGFR) tyrosine kinases inhibitors (TKIs) has been shown to reduce the size of advanced non-small cell lung cancer; however, with Gefitinib and The sensitivity of TKIs treated by Erlotinib was significantly correlated with EGFR gene mutation. The study confirmed that the most common occurrence of EGFR deletion mutations in Region 19 and 21 point mutations lead to changes in the corresponding amino acid sequence and EGFR structure is its main mechanism to increase drug sensitivity. In addition, EGFR gene amplification and CA repeat polymorphism, EGFR pathway downstream signals (such as p-AKT, etc.) activation, HER2 and / or HER3 expression increased, K-RAS gene mutation and other factors affect the TKIs Therapeutic sensitivity. In view of this, further studies on the function of different EGFR mutations and looking for the factors that can predict the therapeutic sensitivity of TKIs, and as a screening index for TKIs sensitive patients, are of great significance for improving the efficacy of TKIs targeted therapy in patients with advanced lung cancer.