Evidence map›Paper›PMID 42036667›Full record

ArticleBreast cancer research : BCR2026

Cetirizine suppresses cancer-associated fibroblast-mediated fibrotic remodeling and epithelial-mesenchymal transition via histamine H

Aya Sasaki, Masahiro Hosonuma, Yuki Maruyama, Eiji Funayama, Hitoshi Toyoda, Toshiaki Tsurui, Kohei Tajima, Rie Nakashima, Yoshitaka Yamazaki, Akira Orimo and 3 more

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Article in Breast cancer research : BCR, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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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

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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

13 authors.

Aya SasakiDepartment of Clinical Immuno Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa Medical University, 6-11-11 Kita-karasuyama, Setagaya-ku, Tokyo, 157-8577, Japan.
Masahiro HosonumaDepartment of Clinical Immuno Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa Medical University, 6-11-11 Kita-karasuyama, Setagaya-ku, Tokyo, 157-8577, Japan.
Yuki MaruyamaDepartment of Clinical Immuno Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa Medical University, 6-11-11 Kita-karasuyama, Setagaya-ku, Tokyo, 157-8577, Japan.
Eiji FunayamaDivision of Medical Pharmacology, Department of Pharmacology, Showa Medical University School of Medicine, Tokyo, Japan.
Hitoshi ToyodaDepartment of Clinical Immuno Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa Medical University, 6-11-11 Kita-karasuyama, Setagaya-ku, Tokyo, 157-8577, Japan.
Toshiaki TsuruiDepartment of Clinical Immuno Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa Medical University, 6-11-11 Kita-karasuyama, Setagaya-ku, Tokyo, 157-8577, Japan.
Kohei TajimaDepartment of Clinical Immuno Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa Medical University, 6-11-11 Kita-karasuyama, Setagaya-ku, Tokyo, 157-8577, Japan.
Rie NakashimaDepartment of Clinical Immuno Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa Medical University, 6-11-11 Kita-karasuyama, Setagaya-ku, Tokyo, 157-8577, Japan.
Yoshitaka YamazakiPharmacological Research Center, Showa Medical University, Tokyo, Japan.
Akira OrimoDepartment of Molecular Pathogenesis, Juntendo University Graduate School of Medicine, Tokyo, Japan.
Tatsunori OguchiDivision of Medical Pharmacology, Department of Pharmacology, Showa Medical University School of Medicine, Tokyo, Japan.
Kiyoshi YoshimuraDepartment of Clinical Immuno Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa Medical University, 6-11-11 Kita-karasuyama, Setagaya-ku, Tokyo, 157-8577, Japan.
Atsuo KuramasuDepartment of Clinical Immuno Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa Medical University, 6-11-11 Kita-karasuyama, Setagaya-ku, Tokyo, 157-8577, Japan. atsuok@med.showa-u.ac.jp.

Funding

Japan Society for the Promotion of Science 22K08902
6 · The paper itself

Abstract

backgroundTriple-negative breast cancer (TNBC) is an aggressive subtype characterized by high metastatic potential and limited therapeutic options. Cancer-associated fibroblasts (CAFs) promote epithelial–mesenchymal transition (EMT) and metastatic progression through extracellular matrix (ECM) remodeling and TGF-β signaling; however, the role of histamine H1 receptor (H1R) signaling in CAFs remains unclear. This study investigated whether cetirizine, a clinically approved second-generation H1R antagonist, modulates CAF function and suppresses metastasis in TNBC.

methodsSyngeneic 4T1 mouse models were used to evaluate the effects of cetirizine on tumor growth and metastasis. Bulk RNA sequencing and pathway analyses were performed on tumor tissues. Human breast cancer–derived CAFs were analyzed for H1R-dependent signaling, gene expression, and cytokine production. Non-contact co-culture assays were used to assess CAF-induced migration and EMT in 4T1 cells.

resultsCetirizine improved survival in a subcutaneous TNBC model but had no effect in a lung colonization model, indicating suppression of early metastatic processes. Transcriptomic analyses revealed downregulation of ECM remodeling and fibrotic pathways. In CAFs, cetirizine inhibited H1R-dependent calcium signaling and suppressed expression of ECM genes (COL1A1, COL3A1, FN1, HSPG2) and TGFB1. These effects persisted under histamine-depleted conditions and were abolished by HRH1 knockdown, supporting inverse agonist activity. Functionally, cetirizine inhibited CAF-induced migration and EMT marker expression in 4T1 cells without direct effects on tumor cells in monoculture.

conclusionsCetirizine suppresses CAF-mediated fibrotic remodeling and EMT through H1R-dependent mechanisms, likely via inverse agonism. By targeting stromal components of the tumor microenvironment, cetirizine may represent a practical repurposing strategy for preventing early metastatic progression in TNBC.

Indexed as

Cancer-Associated FibroblastsCetirizineEpithelial-Mesenchymal TransitionHistamine H1 AntagonistsReceptors, Histamine H1Triple Negative Breast NeoplasmsAnimalsCell Line, TumorCell MovementDisease Models, AnimalFemaleFibrosisGene Expression Regulation, NeoplasticHumansMiceSignal TransductionCetirizineHistamine H1 AntagonistsReceptors, Histamine H1Cancer-associated fibroblastsCetirizineEpithelial–mesenchymal transitionHistamine H1 receptorTriple-negative breast cancer

Identifiers

PMID42036667
PMCPMC13285043

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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.