Mechanistic analysis of hand-foot syndrome associated with kinase inhibitors

2013 Fiscal Year Final Research Report

• Project/Area Number: 24659069
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Medical pharmacy
• Research Institution: The University of Tokyo
• Principal Investigator: SUZUKI Hiroshi 東京大学, 医学部附属病院, 教授 (80206523)
• Co-Investigator(Renkei-kenkyūsha): HONMA Masashi 東京大学, 医学部附属病院, 助教 (60401072)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Keywords: 薬剤反応性 / 薬理学 / シグナル伝達 / 癌 / 生体分子

Research Abstract

Hand-foot syndrome is an adverse reaction frequently observed in patients administering some tyrosine kinase inhibitors (TKIs), which sometimes becomes too severe to continue the therapy. Although we had originally hypothesized that the syndrome is caused by a single inhibition of FLT3, this hypothesis turned out to be implausible when we considered the information of newly developed TKIs which became available after the start of this research. Analyses based on currently up to date information have suggested that VEGR inhibition is a common factor for the syndrome and that simultaneous inhibitions of CSF1R and VEGFR suppress the onset. On the other hand, FLT3 inhibition was considered to negate the suppressive effect against the onset which could be achieved by CSF1R inhibition.