Pulmonary dysfunction as adverse effect is attributed to the inhibition of the novel gefitinib target GAK.

Research Project

Project/Area Number	24700978
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Tumor biology
Research Institution	Osaka University
Principal Investigator	NAITO Yoko 大阪大学, 免疫学フロンティア研究センター, 特任研究員 (10553026)
Project Period (FY)	2012-04-01 – 2014-03-31
Project Status	Completed (Fiscal Year 2013)
Budget Amount *help	¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000) Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000) Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords	ゲフィチニブ / 腫瘍抑制 / 間質性肺炎 / GAK / 癌抑制 / キナーゼ
Research Abstract	The aim of this study is to reveal the mechanism by which gefitinib (iressa), an inhibitor of epithelial growth factor receptor (EGFR), suppress tumor progression and cause pulmonary alveolar dysfunction as adverse effect. We found that gefitinib inhibited GAK kinase activity and inhibition of GAK activity caused dysregulation of EGF-EGFR signaling by aberrant controlling of phosphorylation and endocytosis. We clarified that GAK expression was increased in several cancer and inhibition of GAK suppressed cancer progression by inducing apoptosis. These results may be useful for development of a gefitinib-drived drug which prevent side effect associated with gefitinib therapy and have a more beneficial effect on tumor suppression.