Detection of trifluridine in tumors of patients with metastatic colorectal cancer treated with trifluridine/tipiracil

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K15282
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Kyushu University
• Principal Investigator: NAKANISHI Ryota 九州大学, 医学研究院, 共同研究員 (90771254)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: rifluridine/tipiracil / colorectal cancer / chemosensitivity / Pharmacokinetics

Outline of Final Research Achievements

We aimed to assess the working mechanism of trifluridine/tipiracil for metastatic colorectal cancer. Tumors and normal tissue specimens were obtained from metastatic colorectal cancer patients who were administered FTD/TPI. On the other hand, tumors and bone marrow were resected from mice with peritoneal dissemination treated with FTD/TPI. To detect FTD incorporated into DNA, immunohistochemical staining was performed with newly discovered anti-FTD antibody. FTD was detected in metastatic tumors obtained from mCRC patients who were administered FTD/TPI. In a peritoneal dissemination mouse model, FTD was still detected longer in tumors than in bone marrow after the cessation of FTD/TPI treatment. These results indicate that FTD persists longer in tumors than in bone marrow, which may cause a sustained antitumor effect with tolerable hematotoxicity. We reported this result to a international peer-reviewed journal (Cancer Chemotherapy and Pharmacology: impact factor 3.008).

Free Research Field

大腸癌

Academic Significance and Societal Importance of the Research Achievements

本研究は癌組織（肝転移巣、リンパ節転移巣、腹膜播種巣）の核内に抗癌剤の有効成分を直接同定でき、さらにその経時的な発現の変化を記述した初めての報告となった。また正常組織における評価も行うことで癌部と非癌部における薬物動態の違いを評価できている。これらの結果よりTFTD(ロンサーフ)が非癌部(末梢血内)よりも癌組織において長期にとどまり、血液毒性と抗腫瘍効果に関わる薬物動態についての新知見となった。