Establishment of quantitation method for proteome-based phospho-signaling pathway and its application for prediction of drug effect monitoring

2015 Fiscal Year Final Research Report

• Project/Area Number: 25290054
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Tumor diagnostics
• Research Institution: National Institutes of Biomedical Innovation, Health and Nutrition
• Principal Investigator: Tomonaga Takeshi 国立研究開発法人医薬基盤・健康・栄養研究所, プロテオームリサーチプロジェクト, プロジェクトリーダー (80227644)
• Co-Investigator(Kenkyū-buntansha): ISHIHAMA Yasushi 京都大学, 薬学部, 教授 (30439244) ; MATSUBARA Hisahiro 千葉大学, 医学研究院, 教授 (20282486)
• Co-Investigator(Renkei-kenkyūsha): NAGAYAMA Satoshi 公益財団法人がん研究会, 有明病院消化器外科, 医長 (70362499)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: リン酸化プロテオミクス / 薬効予測 / EGFR阻害剤 / 肺がん

Outline of Final Research Achievements

Molecular target drugs such as kinase inhibitors for cancer treatment are not uniformly clinically effective, thus sorting the patients that will benefit from the treatments is critical. Moreover, acquired resistance for the drugs is also a critical problem. Therefore, the identification of mechanisms underlying the resistance is urgent need. Systematic quantification of kinase activation is potentially predictive of the response of kinase inhibitors and it can be quantitated by phosphorylation level of their substrates. In this study, we developed a large-scale phosphoproteome quantification method for the kinase substrates and applied for prediction of the kinase activities and drug response. We also examined the mechanism of drug resistance. By the phosphoproteome analysis of several lung cancer cell lines which are sensitive or resistant for the drug currently used in clinic, erlotinib, we identified several phosphoproteins and kinases which are able to predict drug sensitivity.

Free Research Field

プロテオミクス　分子腫瘍学