Metabolic adaptation in drug resistance

2021 Fiscal Year Final Research Report

• Project Area: Transomic Analysis of Metabolic Adaptation
• Project/Area Number: 17H06303
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Osaka University
• Principal Investigator: Matsuda Fumio 大阪大学, 情報科学研究科, 教授 (50462734)
• Project Period (FY): 2017-06-30 – 2022-03-31
• Keywords: 代謝アダプテーション / 代謝フラックス解析 / 薬剤耐性 / 好気的解糖 / 酸化的リン酸化

Outline of Final Research Achievements

The development of resistance against anticancer and other drugs has become a problem. In this study, metabolic measurements of cancer cells were carried out to clarify the involvement of energy metabolism in the development of drug resistance. We found that the balance between two energy acquisition pathways - respiration in the mitochondria and aerobic glycolysis in the cytoplasm - is important for drug resistance. Disrupting this balance is expected to be a new approach to avoid the development of drug resistance.

Free Research Field

代謝工学

Academic Significance and Societal Importance of the Research Achievements

抗がん剤などの薬剤は細胞内代謝を擾乱するが、細胞はその影響を打ち消す恒常性を維持することで、薬剤耐性を示すと考えられている。本研究では、代謝流束（フラックス）の測定によりエネルギー代謝の代謝恒常性維持機構の解明を試み、ATP再生経路の補完的な制御が耐性獲得に寄与することを見出した。さらに、代謝フラックスと他のオミクスデータを組み合わせて動的代謝数理モデルの機械学習を行う新たな代謝解析手法を開発した。