Evidence map›Paper›PMID 25230742›Full record

ArticleOncology reports2014

Repeated oral dosing of TAS-102 confers high trifluridine incorporation into DNA and sustained antitumor activity in mouse models.

Nozomu Tanaka, Kazuki Sakamoto, Hiroyuki Okabe, Akio Fujioka, Keisuke Yamamura, Fumio Nakagawa, Hideki Nagase, Tatsushi Yokogawa, Kei Oguchi, Keiji Ishida and 4 more

Open access · hybridAbstract read
In one paragraph

Article in Oncology reports, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
80citing papers in PubMed, 2 pooled it
7.3field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

80 citing papers in PubMed, 2 syntheses or guidelines pooled it, 140 citations in OpenAlex.

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  16. Impact of renal function on non-hematologic toxicities in mCRC patients treated with TAS-102: a post-hoc analysis of the JASCC-CINV2001 study.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2025
    Observational
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20 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 1 institution in 1 country.

Nozomu TanakaTaiho Pharmaceutical Co., Ltd., Tsukuba Research Center, Tsukuba, Ibaraki 300-2611, Japan.
Kazuki SakamotoTaiho Pharmaceutical Co., Ltd., Tsukuba Research Center, Tsukuba, Ibaraki 300-2611, Japan.
Hiroyuki OkabeTaiho Pharmaceutical Co., Ltd., Tsukuba Research Center, Tsukuba, Ibaraki 300-2611, Japan.
Akio FujiokaTaiho Pharmaceutical Co., Ltd., Tsukuba Research Center, Tsukuba, Ibaraki 300-2611, Japan.
Keisuke YamamuraTaiho Pharmaceutical Co., Ltd., Tsukuba Research Center, Tsukuba, Ibaraki 300-2611, Japan.
Fumio NakagawaTaiho Pharmaceutical Co., Ltd., Tokushima Research Center, Ebisuno, Hiraishi, Kawauchi-cho, Tokushima 771-0194, Japan.
Hideki NagaseTaiho Pharmaceutical Co., Ltd., Tokushima Research Center, Ebisuno, Hiraishi, Kawauchi-cho, Tokushima 771-0194, Japan.
Tatsushi YokogawaTaiho Pharmaceutical Co., Ltd., Tsukuba Research Center, Tsukuba, Ibaraki 300-2611, Japan.
Kei OguchiTaiho Pharmaceutical Co., Ltd., Tsukuba Research Center, Tsukuba, Ibaraki 300-2611, Japan.
Keiji IshidaTaiho Pharmaceutical Co., Ltd., Tsukuba Research Center, Tsukuba, Ibaraki 300-2611, Japan.
Akiko OsadaTaiho Pharmaceutical Co., Ltd., Tsukuba Research Center, Tsukuba, Ibaraki 300-2611, Japan.
Hiromi KazunoTaiho Pharmaceutical Co., Ltd., Tsukuba Research Center, Tsukuba, Ibaraki 300-2611, Japan.
Yukari YamadaTaiho Pharmaceutical Co., Ltd., Tsukuba Research Center, Tsukuba, Ibaraki 300-2611, Japan.
Kenichi MatsuoTaiho Pharmaceutical Co., Ltd., Tsukuba Research Center, Tsukuba, Ibaraki 300-2611, Japan.
Taiho Pharmaceutical (Japan) · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

TAS-102 is a novel oral nucleoside antitumor agent containing trifluridine (FTD) and tipiracil hydrochloride (TPI). The compound improves overall survival of colorectal cancer (CRC) patients who are insensitive to standard chemotherapies. FTD possesses direct antitumor activity since it inhibits thymidylate synthase (TS) and is itself incorporated into DNA. However, the precise mechanisms underlying the incorporation into DNA and the inhibition of TS remain unclear. We found that FTD-dependent inhibition of TS was similar to that elicited by fluorodeoxyuridine (FdUrd), another clinically used nucleoside analog. However, washout experiments revealed that FTD-dependent inhibition of TS declined rapidly, whereas FdUrd activity persisted. The incorporation of FTD into DNA was significantly higher than that of other antitumor nucleosides. Additionally, orally administered FTD had increased antitumor activity and was incorporated into DNA more effectively than continuously infused FTD. When TAS-102 was administered, FTD gradually accumulated in tumor cell DNA, in a TPI-independent manner, and significantly delayed tumor growth and prolonged survival, compared to treatment with 5-FU derivatives. TAS-102 reduced the Ki-67-positive cell fraction, and swollen nuclei were observed in treated tumor tissue. The amount of FTD incorporation in DNA and the antitumor activity of TAS-102 in xenograft models were positively and significantly correlated. These results suggest that TAS-102 exerts its antitumor activity predominantly due to its DNA incorporation, rather than as a result of TS inhibition. The persistence of FTD in the DNA of tumor cells treated with TAS-102 may underlie its ability to prolong survival in cancer patients.

Indexed as

Administration, OralAnimalsAntineoplastic AgentsCell Line, TumorCell ProliferationColonic NeoplasmsDNA, NeoplasmDrug CombinationsMaleMice, Inbred BALB CMice, NudePyrrolidinesThymineTrifluridineUracilXenograft Model Antitumor AssaysAntineoplastic AgentsDNA, NeoplasmDrug CombinationsPyrrolidinesThymineTrifluridinetrifluridine tipiracil drug combinationUracil

Identifiers

PMID25230742
PMCPMC4240496
OpenAlexW2045370737

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.