Reverse omics analysis for mechanisms on hand-foot syndrome and predictive system construction.

2014 Fiscal Year Final Research Report

• Project/Area Number: 24659078
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Medical pharmacy
• Research Institution: National Institute of Health Sciences
• Principal Investigator: SAITO Yoshiro 国立医薬品食品衛生研究所, 医薬安全科学部, 部長 (50215571)
• Co-Investigator(Kenkyū-buntansha): MAEKAWA Keiko 国立医薬品食品衛生研究所, 医薬安全科学部, 室長 (70270626) ; KONDO Shunsuke 国立がん研究センター中央病院, 肝胆膵内科, 医員 (90546201)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 副作用 / 抗がん剤

Outline of Final Research Achievements

Metabolome, vast majority of endobiotic metabolites, is the most down-stream of omics layers and close to phenotype including drug adverse reactions. Purpose of this study is to reveal onset mechanisms of molecularly-targeted drug-related hand-foot syndrome, using mainly metabolomic analysis and upstream genomics. First, metabolomic analysis was performed with extracts from human A431 cell line treated with sorafenib and sunitinib (likely to cause the syndrome) as well as imatinib and gefitinib (unlikely to cause the syndrome). Among the measured lipids, a diacylglycerol was significantly changed by sorafenib and sunitinib, but not by imatinib and gefinitib. Based on this result, protein kinase C was suggested to be involved in the onset of hand-foot syndrome. Since recruiting sorafenib-administered patients have been continuing, genomic and metabolomic analyses of patient samples have not been obtained the final results and would be publicized it near future.

Free Research Field

医薬品安全性学