Elucidation of factors associating with chemoresistance in EGFR-TKI resistant lung adenocarcinoma

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K19073
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Human pathology
• Research Institution: Tohoku University
• Principal Investigator: Saito Ryoko 東北大学, 医学系研究科, 助教 (30733349)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: lung adenocarcinoma / EGFR-TKI resistance / chemoresistance / HIF-1α / p22phox

Outline of Final Research Achievements

Chemotherapy is broadly used for the patients with　EGFR-TKI (epidermal growth factor receptor-tyrosine kinase inhibitors) resistant lung adenocarcinoma. This study aimed to elucidate the mechanism associating with chemoresistance and EGFR-TKI resistance. According to the microarray using EGFR-TKI resistant lung adenocarcinoma cell line, we postulated that p22phox/ HIF-1α (hypoxia inducible factor-1α) pathway might be result in chemoresistance and EGFR-TKI resistance via induction of EMT (epithelial-mesenchymal transition). Our study showed that p22phox and HIF-1α expressions were elevated in some EGFR-TKI resistant lung adenocarcinoma cell line, and that in these cell line p22phox induced HIF-1α gene expression following to induction of EMT and chemoresistance. Our results may provide the first evidence that targeting p22phox/ HIF-1α could be a new therapeutic strategy to enhance the chemosensitivity in EGFR-TKI resistant lung adenocarcinoma.

Free Research Field

人体病理学