Analysis of copper distribution by X-ray fluorescence analysis and platinum preparation resistance mechanism by copper transporters

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K18091
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Kyushu University
• Principal Investigator: HORIOKA Kohei 九州大学, 医学研究院, 共同研究員 (10783699)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: 大腸癌 / 白金製剤 / 治療抵抗性 / oxaliplatin / 銅輸送体 / 蛍光X線分析 / SPring-8

Outline of Final Research Achievements

Oxaliplatin is a key drug in the treatment of colorectal cancer, but drug resistance is a problem. The purpose of this study is to elucidate the intratumoral dynamics of drugs and the role of copper transporters in their dynamics by using fluorescent X-ray analysis to predict therapeutic responsiveness and elucidate the mechanism of resistance.
The distribution of essential elements in the living body in the tumor tissue could be visualized and quantified by using fluorescent X-ray analysis using SPring-8. In the principal component analysis of the distribution in the tumor tissue, only copper tended to have a different distribution in the treatment-effective cases than in the ineffective cases, and the group with therapeutic effect showed a positive correlation with platinum, and the group with poor therapeutic response showed a negative correlation with platinum.

Free Research Field

医歯薬学

Academic Significance and Societal Importance of the Research Achievements

本研究は、蛍光X線分析という工学的アプローチを用いて、oxaliplatinを投与した大腸癌の腫瘍組織中の銅の局所かつ微量な分布を可視化することで、抗癌剤の腫瘍内動態や銅輸送体の役割を明らかにする手掛かりとなった。
今後も工学及び薬学に携わる研究者とも連携し、臨床情報や抗腫瘍効果との関連を調査することで、oxaliplatinを用いた化学療法に対する個々の治療反応性を予測し、さらには耐性獲得の機序の解明を引き続き試みる。本研究の成果は白金錯体系抗腫瘍薬の治療効果の改善や副作用の軽減につながるものと期待される。