The study for the mechanism of 5FU-resistance based on the metabolism of 5FU inbreast cancer cells

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K09090
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55010:General surgery and pediatric surgery-related
• Research Institution: Gifu University
• Principal Investigator: mori ryutaro 岐阜大学, 医学部附属病院, 准教授 (00738635)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 乳癌 / 5FU / 耐性 / Thymidine phosphorylase

Outline of Final Research Achievements

The importance of 5FU in the treatment of breast cancer has been increasing recently. Therefore, we investigated the mechanism underlying the resistance to 5FU, focusing on the changes in the 5FU metabolism using breast cancer cell lines, and found that in 5FU-resistant cells, the metabolism of 5FU changed to decrease the intracellular levels of fluoro-uridine monophosphate (FdUMP), which is the active metabolite of 5FU, and to increase the synthesis of thymidylate. We also found that the resistance to 5FU in 5FU-resistant cells was reversed by the inhibition of TP by tipiracil. Tipiracil is a component of TAS-102, the anti-cancer drug for metastatic colorectal and gastric cancer and has been already used in clinical practice. Therefore, combination therapy with 5FU and tipiracil would be easy to incorporate, and we believe it will be a promising therapy for breast cancer.

Free Research Field

腫瘍外科

Academic Significance and Societal Importance of the Research Achievements

5FU製剤は乳癌をはじめ様々な癌の治療で使用されており5FUの獲得耐性が問題となっている。今回の研究では5FU耐性はTipiracilを併用することにより克服できることが明らかになり、またTipiracilはすでに臨床で使用されている薬剤であり安全性が確認されていることから、5FUとTipiracilの併用療法が癌治療の発展に貢献すると考える。