Prediction of molecular target drug effect using quantitative phosphoproteome analysis of patient derived colorectal cancer cells

2015 Fiscal Year Final Research Report

• Project/Area Number: 26670614
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• 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)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: リン酸化プロテオミクス / 薬効予測 / EGFR抗体 / 大腸がん

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, cetuximab, 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