Mechanistic analysis of hand-foot syndrome associated with kinase inhibitors

手足综合征是一种常见的不良反应，患者使用一些酪氨酸激酶抑制剂(TKIs)，有时会变得太严重而无法继续治疗。虽然我们最初假设该综合征是由Flt3的单一抑制引起的，但当我们考虑到在本研究开始后获得的新开发的TKI的信息时，这一假设被证明是不可信的。基于最新信息的分析表明，VEGR抑制是该综合征的共同因素，CSF1R和VEGFR的同时抑制抑制了该综合征的发病。另一方面，对Flt3的抑制被认为可以抵消CSF1R抑制对发病的抑制作用。

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.