Monitoring trifluridine incorporation in the peripheral blood mononuclear cells of colorectal cancer patients under trifluridine/tipiracil medication

Ryota Nakanishi, Hiroyuki Kitao, Mamoru Kiniwa, Yosuke Morodomi, Makoto Iimori, Junji Kurashige, Masahiko Sugiyama, Yuichiro Nakashima, Hiroshi Saeki, Eiji Oki, Yoshihiko Maehara

研究成果: Contribution to journalArticle査読

4 被引用数 (Scopus)

抄録

Trifluridine/tipiracil (TFTD, TAS-102) is an orally administrated anti-cancer drug with efficacy validated for patients with metastatic colorectal cancer (mCRC). Trifluridine (FTD) is an active cytotoxic component of TFTD and mediates the anticancer effect via its incorporation into DNA. However, it has not been examined whether FTD is incorporated into the tissues of patients who received TFTD medication. By detecting FTD incorporation into DNA by a specific antibody, we successfully detected FTD in the bone marrow and spleen cells isolated from FTD-challenged mice as well as human peripheral blood mononuclear cells (PBMCs) activated with phytohemagglutinin-P and exposed to FTD in vitro. FTD was also detected in PBMCs isolated from mCRC patients who had administrated TFTD medication. Intriguingly, weekly evaluation of PBMCs from mCRC patients revealed the percentage of FTD-positive PBMCs increased and decreased in parallel with the administration and cessation of TFTD medication, respectively. To our knowledge, this is the first report to detect an active cytotoxic component of a chemotherapeutic drug in clinical specimens using a specific antibody. This technique may enable us to predict the clinical benefits or the adverse effects of TFTD in mCRC patients.

本文言語英語
論文番号16969
ジャーナルScientific reports
7
1
DOI
出版ステータス出版済み - 12 1 2017

All Science Journal Classification (ASJC) codes

  • 一般

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