Elucidation of the mechanism of acquisition of anticancer drug resistance caused by mitochondrial disorders

2021 Fiscal Year Final Research Report

• Project/Area Number: 21K20808
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0901:Oncology and related fields
• Research Institution: Nara Medical University
• Principal Investigator: Mori Shiori 奈良県立医科大学, 医学部, 助教 (00907032)
• Project Period (FY): 2021-08-30 – 2022-03-31
• Keywords: 抗がん剤耐性 / ミトコンドリア / ρ0形質 / 幹細胞性 / ROS / 悪液質

Outline of Final Research Achievements

Anticancer drug resistance is one of the key barriers in cancer therapy. Recently involvement of mitochondria in anticancer drug resistance has been focused. In this study, we established cancer cells with mitochondrial DNA damage to analyze their characteristics. We found that cancer cells partially damaged in mitochondrial DNA (partial ρ0 cells) showed increased pro-inflammatory effects and induced cachexia, along with decreased proliferative capacity, oxygen consumption and stemness, and increased ROS production. They also showed anticancer drug resistance. Since cancer cells acquired partial ρ0 phenotype upon continuous treatment with anticancer drugs, this is a new mechanism for the acquisition of anticancer drug resistance.

Free Research Field

実験病理

Academic Significance and Societal Importance of the Research Achievements

化学療法によって誘導されるミトコンドリア障害が抗がん剤抵抗性を誘導することが明らかになった。抗がん剤によるミトコンドリアDNAの障害が抗がん剤耐性をもたらすことは、ほとんどの抗がん剤において一般的に生じ得る抗がん剤耐性獲得機序であり、がん治療において重要な知見と見なされる。今後この新たな耐性抑制の標的を抽出し治療戦略に結びつけることが出来れば、がん化学療法における大きな進展となり、癌患者の予後改善をもたらすと期待される。