Basic and clinical study of EGFR gene mutation-positive lung cancer using a genetically modified mouse

2014 Fiscal Year Final Research Report

• Project/Area Number: 23390221
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Okayama University
• Principal Investigator: KIURA Katsuyuki 岡山大学, 大学病院, 教授 (10243502)
• Co-Investigator(Kenkyū-buntansha): TKIGAWA Nagio 川崎医科大学, 医学部, 教授 (60325107) ; HOTTA Katsuyuki 岡山大学, 大学病院, 講師 (70379816)
• Co-Investigator(Renkei-kenkyūsha): TAKATA Minoru 京都大学, 放射線生物研究センター, 教授 (30281728) ; NAKABEPPU Yusaku 九州大, 学生体防御医学研究所, 教授 (30180350) ; YOSHINO Tadashi 岡山大学, 医薬歯学総合研究科, 教授 (70183704)
• Project Period (FY): 2011-04-01 – 2015-03-31
• Keywords: EGFR遺伝子改変マウス / afatinib / everolimus (mTOR阻害薬), / JAK-1/2 inhibitors / cetuximab / bevacizumab / Ogg1ホモノックアウトマウス / NNK

Outline of Final Research Achievements

① Using the EGFR genetically modified mice, afatinib (irreversible TKI), everolimus (mTOR inhibitor), and AZD1480 (JAK-1/2 inhibitors) revealed an anti-tumor effect. ②In mouse xenograft models, afatinib + cetuximab + bevacizumab combination therapy against resistant cells harbouring T790M has proved to result in lasting pathologic complete response. ③ Although 9.3% of Ogg1 (-/-) homozygous knockout mice to a high dose of tobacco-specific nitrosamines (NNK) had adenocarcinoma of the lung, it is not recognized carcinogenesis at low doses. The relationship between epidermal growth factor receptor (EGFR) gene mutations and NNK-induced carcinogenesis was unclear.

Free Research Field

呼吸器内科学（胸部腫瘍学）