Novel molecular mechanisms of acquired resistance to gefitinib in lung adenocarcinoma

2014 Fiscal Year Final Research Report

• Project/Area Number: 25830111
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor therapeutics
• Research Institution: Kanazawa University
• Principal Investigator: NAKATA Asuka 金沢大学, がん進展制御研究所, 助教 (70597921)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: 肺腺癌 / イレッサ

Outline of Final Research Achievements

Although Iressa (gefitinib) were greatly effective in lung adenocarcinoma patients harboring EGFR mutations, these patients ultimately have acquired resistance to gefitinib. To explore novel molecular mechanisms for gefitinib-resistance, we established the gefitinib-resistant PC9M2 cells that were spontaneously derived from gefitinib-sensitive PC9. Microarray analysis revealed that β－catenin-related genes were upregulated in PC9M2 cells compared with PC9 cells. We next demonstrated that the downregulation of β-catenin partially restored the sensitivity to gefitinib in PC9M2 cells. Using the tissues from lung cancer patients harbored EGFR mutation, we showed that activation of β-catenin was related with gefitinib sensitivity in patient’s samples, suggesting that enhanced β-catenin activation is associated with primary and acquired resistance to gefitinib. Targeting β-catenin pathway may be useful for overcoming the resistance to gefitinib

Free Research Field

腫瘍学