Understanding of the regulation mechanisms of therapy resistance by mTOR complex 2

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K09919
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Kanazawa University
• Principal Investigator: Ueno Masaya 金沢大学, がん進展制御研究所, 助教 (20334766)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 抗がん剤耐性 / 白血病 / 白血病幹細胞

Outline of Final Research Achievements

In order to develop therapeutic methods for cure of leukemia, it is necessary to know the characteristics of leukemia stem cells and identify the important molecules that regulate them. Previously, we studied about the regulation of metabolisms in leukemia stem cells, and we found that mTOR complex 2 (mTORC2) is important for the resistance of leukemia stem cells to anticancer drugs. A functional screening using a CRISPR custom library targeting downstream molecules of mTORC2 revealed that lipid and methionine metabolism are important for anticancer drug resistance in leukemia cells.

Free Research Field

白血病幹細胞

Academic Significance and Societal Importance of the Research Achievements

白血病の根治を目指した治療法の開発には、白血病細胞の特性を知り、その制御を司る重要な分子を特定することが必要である。研究代表者らは、白血病細胞の代謝調節に着目し研究を進め、脂質代謝経路およびメチオニン代謝経路が白血病細胞の抗がん剤耐性に重要であることを明らかにした。これらの知見は、代謝経路の阻害剤と抗がん剤を組み合わせた新たな治療法の確立に貢献することが期待される。