Development of a topical treatment for cutaneous neurofibromatosis type I

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K21653
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 56:Surgery related to the biological and sensory functions and related fields
• Research Institution: Kyoto University
• Principal Investigator: MORIMOTO NAOKI 京都大学, 医学研究科, 教授 (40378641)
• Project Period (FY): 2020-07-30 – 2023-03-31
• Keywords: 神経線維腫

Outline of Final Research Achievements

As a model of neurofibromatosis type I: NF1, we investigated the effects of MEK inhibitor at the cellular level in more detail: the NF1 cell line has persistent ERK activation, proliferation and the MAPK pathway are inhibited by selmetinib (MEK inhibitor), and the optimal concentration required for this was optimal concentrations were determined. As a result, a model for evaluation of MEK pathway inhibition by NF1 cells was established, and the detailed mechanism by which MEK pathway inhibition halts NF1 cell proliferation is becoming clear. Furthermore, we investigated the action in combination with a new inhibitor and found that the combination with the conventional product, selmetinib, showed high inhibition of the MEK pathway.

Free Research Field

細胞内シグナル伝達

Academic Significance and Societal Importance of the Research Achievements

Selmetinib単剤およびGSK690693の併用でのNF1不死化細胞株の細胞増殖への影響について、併用の場合、Selmetinib単剤に比較しERK経路が強く抑制された。今後NF1の治療において、Selmetinibが無効か効果不十分の場合の二剤併用療法や、各薬剤の投与量を抑えながらの治療の可能性を示唆する。