The possibility of cancer therapy targeting to cellular iron metabolism

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K07036
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
• Research Institution: Tokai University
• Principal Investigator: Miyazawa Masaki 東海大学, 健康学部, 准教授 (10554818)
• Co-Investigator(Kenkyū-buntansha): 平林 健一 富山大学, 学術研究部医学系, 教授 (60514388) ; 服部 鮎奈 京都大学, ウイルス・再生医科学研究所, 准教授 (60820420)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: がん / 鉄代謝

Outline of Final Research Achievements

Iron is an essential mineral for maintaining cellular and organismal homeostasis, including cell division and energy production. Recently, we have elucidated that cancer cell death induced by the chemotherapeutic agent cisplatin is also triggered by intracellular iron depletion, independently of its inhibition of DNA replication through DNA binding. Therefore, based on these findings, this project aims to further advance the research by elucidating the molecular mechanisms of cancer cell death induced by iron deficiency. Additionally, the project seeks to establish a practicable and low-side-effect cancer therapy targeting intracellular iron metabolism regulation systems and to lay the groundwork for the development of novel anticancer drugs. The analysis revealed a significant correlation between IRP2 protein levels and patient survival rates in pancreatic cancer, indicating that IRP2 could be a potential target for cancer therapy.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

鉄の欠乏は、貧血をはじめとする栄養障害の原因となる一方で、過剰な鉄は成長因子シグナルの活性化やDNAの酸化傷害を引き起こす活性酸素（ヒドロキシラジカル）の産生原因となり、発がんやがんの悪性化につながる。そのため申請者は、このリスクファクターとなりえる過剰な鉄を標的として、がん治療へ応用することを目標とした。本研究において、鉄の代謝とがん細胞の生存および増殖との関係を分子レベルで解明することで、鉄に関連する新しい医療技術の実用化に貢献できると考えている。