2024 Fiscal Year Final Research Report

Newly developed malignant degree evaluation and metabolic target therapy prediction for breast cancer using proteome and metabolome analysis

Research Project

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Project/Area Number	22K08707
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 55010:General surgery and pediatric surgery-related
Research Institution	Tohoku University
Principal Investigator	Tada Hiroshi 東北大学, 医学系研究科, 准教授 (50436127)
Co-Investigator(Kenkyū-buntansha)	権田幸祐東北大学, 医学系研究科, 教授 (80375435) 石田孝宣東北大学, 医学系研究科, 教授 (00292318) 原田成美東北大学, 大学病院, 助教 (70547413) 北村成史東北大学, 医学系研究科, 准教授 (50624912)
Project Period (FY)	2022-04-01 – 2025-03-31
Keywords	乳癌 / メタボローム
Outline of Final Research Achievements	In this study, we investigated the metabolic characteristics of refractory breast cancer to develop new diagnostic and therapeutic approaches. When the three cell lines were treated with the chemotherapeutic agent doxorubicin, HCC38 showed high sensitivity, whereas MDA‐MB‐231 and MCF‐7 exhibited resistance. In the resistant lines, the mitochondrial membrane potential decreased, and activation of mitophagy suggested a mechanism for suppressing reactive oxygen species. Although HCC38 was glycolysis‐dominant, MDA‐MB‐231 and MCF‐7 were dependent on oxidative phosphorylation. Clinical specimen analysis revealed that DRP1 and Parkin were highly expressed in hormone receptor-negative cases, low expression of p62 was associated with an increased risk of recurrence, and FDG-PET exhibited limitations in its predictive accuracy.
Free Research Field	乳腺外科学
Academic Significance and Societal Importance of the Research Achievements	本研究は、悪性度の高い乳がんが薬剤耐性を示す新たなメカニズムを明らかにしたものです。薬剤が効きにくい乳癌細胞では、従来多くのがん細胞が利用する糖代謝（グリコリシス）とは異なり、ミトコンドリアの酸化リン酸化でエネルギーを生成し、さらにミトコンドリアを分解・再利用するマイトファジー機構で薬剤ダメージを抑制していました。この特徴は、FDG-PETなどの従来画像診断では把握しづらい代謝様式であり、悪性度の高い乳がんの薬剤耐性を理解する学術的意義があります。これらミトコンドリア機能を標的とした新規診断法や治療薬の開発は、難治性TNBC患者の治療成績向上に繋がると期待されます。