2022 Fiscal Year Final Research Report

Development of chemoradiotherapy using TAS-102 for rectal cancer

Research Project

PDF

Project/Area Number	20K09051
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 55020:Digestive surgery-related
Research Institution	Research Institute for Clinical Oncology Saitama Cancer Center
Principal Investigator	Nishikawa Takeshi 地方独立行政法人埼玉県立病院機構埼玉県立がんセンター(臨床腫瘍研究所), 病院消化器外科, 医長 (00749799)
Co-Investigator(Kenkyū-buntansha)	石原聡一郎東京大学, 医学部附属病院, 教授 (00376443) 野澤宏彰東京大学, 医学部附属病院, 准教授 (80529173) 川合一茂東京大学, 医学部附属病院, 届出研究員 (80571942)
Project Period (FY)	2020-04-01 – 2023-03-31
Keywords	Trifluridine / 放射線療法 / 大腸癌
Outline of Final Research Achievements	Using the HT-29 colon cancer cell line, we showed that trifluridine inhibits cell proliferation in colon cancer cells after irradiation with 4 Gy of radiation. Trifluridine also suppressed cell proliferation by arresting the cell cycle at G2/M, but not by increasing apoptosis. Furthermore, the expression of HIF-1α was quantified by western blotting, and it was confirmed that the expression of HIF-1α was increased by irradiation. Trifluridin was added, and it was confirmed that radiation-induced HIF-1α was suppressed.
Free Research Field	下部消化管外科
Academic Significance and Societal Importance of the Research Achievements	直腸癌に対する放射線治療抵抗性の原因の一つにhypoxia - inducible factor (HIF)-1 αの活性化が挙げられるが、TAS-102によってHIF-1αを抑制することで放射線感受性を高めることができる可能性が示唆された。さらにそのメカニズムの一部を解明することで今後の放射線抵抗性の克服に向けたさらなる研究へとつながる重要な成果が得られたと思われる。