Evidence map›Paper›PMID 37724648›Full record

ArticleCancer science2023

Combination therapy with WEE1 inhibition and trifluridine/tipiracil against esophageal squamous cell carcinoma.

Trang H Nguyen Vu, Osamu Kikuchi, Shinya Ohashi, Tomoki Saito, Tomomi Ida, Yukie Nakai, Yang Cao, Yoshihiro Yamamoto, Yuki Kondo, Yosuke Mitani and 6 more

Open access · goldAbstract read
In one paragraph

Article in Cancer science, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.3field-weighted citation impact, top 36% 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

3 citing papers in PubMed, 2 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
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

16 authors at 1 institution in 3 countries.

Trang H Nguyen VuDepartment of Therapeutic Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Osamu KikuchiDepartment of Clinical Bio-Resource Center, Kyoto University Hospital, Kyoto, Japan.
Shinya OhashiDepartment of Therapeutic Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.ORCID https://orcid.org/0000-0003-1776-4309
Tomoki SaitoDepartment of Therapeutic Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Tomomi IdaDepartment of Therapeutic Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Yukie NakaiDepartment of Therapeutic Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Yang CaoDepartment of Therapeutic Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Yoshihiro YamamotoDepartment of Therapeutic Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.ORCID https://orcid.org/0000-0003-0194-9579
Yuki KondoDepartment of Therapeutic Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Yosuke MitaniDepartment of Therapeutic Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.ORCID https://orcid.org/0000-0003-1603-0004
Shigeki KataokaDepartment of Therapeutic Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Tomohiro KondoDepartment of Therapeutic Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.ORCID https://orcid.org/0000-0001-5102-2654
Chikatoshi KatadaDepartment of Therapeutic Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.ORCID https://orcid.org/0000-0002-2713-4661
Atsushi YamadaDepartment of Therapeutic Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Junichi MatsubaraDepartment of Therapeutic Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Manabu MutoDepartment of Therapeutic Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.ORCID https://orcid.org/0000-0002-3127-8203
Kyoto University · JP

Funding

Japan Society for the Promotion of Science 22K07960Taiho Pharmaceutical
6 · The paper itself

Abstract

Despite advanced therapeutics, esophageal squamous cell carcinoma (ESCC) remains one of the deadliest cancers. Here, we propose a novel therapeutic strategy based on synthetic lethality combining trifluridine/tipiracil and MK1775 (WEE1 inhibitor) as a treatment for ESCC. This study demonstrates that trifluridine induces single-strand DNA damage in ESCC cells, as evidenced by phosphorylated replication protein 32. The DNA damage response includes cyclin-dependent kinase 1 (CDK1) (Tyr15) phosphorylation as CDK1 inhibition and a decrease of the proportion of phospho-histone H3 (p-hH3)-positive cells, indicating cell cycle arrest at the G2 phase before mitosis entry. The WEE1 inhibitor remarkedly suppressed CDK1 phosphorylation (Try15) and reactivated CDK1, and also increased the proportion of p-hH3-positive cells, which indicates an increase of the number of cells into mitosis. Trifluridine combined with a WEE1 inhibitor increased trifluridine-mediated DNA damage, namely DNA double-strand breaks, as shown by increased γ-H2AX expression. Moreover, the combination treatment with trifluridine/tipiracil and a WEE1 inhibitor significantly suppressed tumor growth of ESCC-derived xenograft models. Hence, our novel combination treatment with trifluridine/tipiracil and a WEE1 inhibitor is considered a candidate treatment strategy for ESCC.

Indexed as

Esophageal NeoplasmsEsophageal Squamous Cell CarcinomaCell Cycle ProteinsCell Line, TumorHistonesHumansPhosphorylationProtein-Tyrosine KinasesPyrrolidinesThymineTrifluridineCell Cycle ProteinsHistonesProtein-Tyrosine KinasesPyrrolidinesThyminetipiracilTrifluridineWEE1 protein, humanDNA damage responseesophageal squamous cell carcinomasynthetic lethalitytrifluridineWEE1 inhibitor

Identifiers

PMID37724648
PMCPMC10728021
OpenAlexW4386845792

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

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.