2023 Fiscal Year Final Research Report

The new strategy for radioresistance in cancer associated with p53 mutation using targeted alpha therapy

Research Project

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Project/Area Number	20H03633
Research Category	Grant-in-Aid for Scientific Research (B)
Allocation Type	Single-year Grants
Section	一般
Review Section	Basic Section 52040:Radiological sciences-related
Research Institution	National Institutes for Quantum Science and Technology
Principal Investigator	Sakashita Tetsuya 国立研究開発法人量子科学技術研究開発機構, 高崎量子応用研究所量子バイオ基盤研究部, 上席研究員 (30311377)
Co-Investigator(Kenkyū-buntansha)	大島康宏国立研究開発法人量子科学技術研究開発機構, 高崎量子応用研究所量子バイオ基盤研究部, 主幹研究員 (00588676) 松本義久東京工業大学, 科学技術創成研究院, 教授 (20302672) 河野暢明慶應義塾大学, 政策・メディア研究科(藤沢), 准教授 (90647356) 有田隆也名古屋大学, 情報学研究科, 教授 (40202759) 横田裕一郎国立研究開発法人量子科学技術研究開発機構, 高崎量子応用研究所放射線生物応用研究部, 主幹研究員 (30391288)
Project Period (FY)	2020-04-01 – 2024-03-31
Keywords	標的アイソトープ治療 / p53 / アルファ線 / 悪性褐色細胞腫
Outline of Final Research Achievements	In order to clarify the therapeutic effect and mechanism for p53 mutations, we carried out the following: 1) construction of cell lines by genome editing, 2) examination of 211At-MABG addition conditions, 3) analysis of the cell-killing effect, and 4) animal experiments. When constructing new cell lines, colony isolation was difficult. Examination of 211At-MABG addition conditions was carried out on existing cell lines. We encountered difficulties along the way, such as losing a co-researcher in an accident, and were unable to fully analyze the cytocidal effect or conduct animal experiments. However, we performed single-cell analysis on samples that could be obtained, and in addition, we introduced a colony formation assay that allows for precise measurement of viability and succeeded in obtaining a special survival-curve. Finally, we were able to obtain samples of existing cell lines necessary for analysis of the cell-killing effect.
Free Research Field	線量評価、放射線生物学
Academic Significance and Societal Importance of the Research Achievements	p53変異に対する治療効果とメカニズムを明らかにできれば、今後の治療履歴により生ずる可能性がある、がんのα線放出RI内用療法への治療抵抗性を克服し、さらに治療効果を高める新たな治療戦略に繋がる可能性がある。