Elucidation of the Mechanism of Microtubule Action by Antioxidants and New Clinical Applications

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K16824
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Chiba University
• Principal Investigator: Takada Mamoru 千葉大学, 総合安全衛生管理機構, 助教 (90800392)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 微小管阻害 / 乳癌 / 抗酸化物質

Outline of Final Research Achievements

Microtubule inhibitors are still one of the mainstays of anticancer drugs. Although the results of recent clinical trials of immune checkpoint inhibitors have revealed that microtubule inhibitors are the most useful agents for their combination, no new microtubule inhibitors have been developed. The microtubule inhibitory effect of CMPD1, which is the focus of this study, is several hundred times stronger than that of Taxol, has far fewer adverse events in animal experiments, induces stronger chromosomal instability in cancer cells as its mechanism, and is a drug that can be washed out by drug withdrawal. In addition, the drug is more likely to be washed out in normal cells than in cancer cells. We will aim for clinical application in the future.

Free Research Field

乳腺外科学

Academic Significance and Societal Importance of the Research Achievements

抗がん剤である微小管阻害剤は最も歴史の古い薬剤のうちの一つであるが未だに抗がん剤の主役の一つである。近年の免疫チェックポイント阻害剤の臨床試験の結果から、微小管阻害剤はその併用薬として最も有用な薬剤であることがわかり、その重要性はますます高まっているにもかかわらず、新たな微小管阻害剤開発は進んでいない。本研究において、CMPD1は実臨床で最も広く使用されているTaxolと比較しても非常に有望な新たな微小管阻害剤であること、そしてCMPD１のがん細胞および正常細胞への作用メカニズムがわかってきた。臨床応用に向けて、今最も注目されている微小管阻害剤が及ぼす免疫への作用を明らかにし、開発を目指したい