Analysis of heterogeneity related g factors in carcinogenesis of lung cancer.

几十年来，肺癌一直是世界上最常见的癌症，其预后目前是不可接受的。肺腺癌中表皮生长因子受体（EGFR）基因的激活突变与EGFR-酪氨酸激酶抑制剂（TKI）的显著临床反应相关。然而，患者经常会复发。然而，关于获得性耐药的整体情况和生物学意义仍不清楚。在这项研究中。本实验拟利用肺癌细胞系，通过共培养法测定肿瘤生长势，研究混合比例与EGFR-TKI耐药性的关系，建立瞬时稳定转移GFR基因的癌细胞可视化。我们还研究了腺鳞状细胞癌的临床特征，作为肿瘤异质性的代表性模型。此外，我们的研究结果表明，各种基因或蛋白质表达的改变可以解释所有的耐药机制，这一现象表明，获得性耐药相关基因之间存在复杂的关系。我们还报道了T790M可能因此是预测EGFR-TKI治疗的日本患者预后良好的有用标记物。

Lung cancer has been the most common cancer in the world for several decades and the prognosis is currently unacceptable. Activating mutations in the epidermal growth factor receptor(EGFR) gene in lung adenocarcinoma are associated with a dramatic clinical response to EGFR-tyrosine kinase inhibitors(TKI). However, patients often experience a relapse. However, the whole picture and biological significance regarding acquired resistance remains unclear. in this research. We planned the experiment to establish the visualization for the cancer cell transferred for GFR gene transiently and stably by using lung cancer cell lines, measurement for tumor growth potential by co-culture, and investigation of relationship between mix ratio and drug resistance to EGFR-TKI. We also examined the clinical feature of adenosquamous cell carcinoma as a representative model for heterogeneity of the tumor. Furtherer, our results showed that various alterations in gene or protein expression can account for all resistant mechanisms and this phenomenon suggests the existence of complicated relationships among acquired resistance-related genes. We also reported that T790M may thus be a useful marker for predicting a favorable prognosis in Japanese patients treated by an EGFR-TKI.