Evidence map›Paper›PMID 42222149›Full record

ArticleFrontiers in pharmacology2026

EZH2 blockade reverses doxorubicin resistance by inducing metabolic vulnerability and enhancing DNA damage in breast cancer.

Xiaomin Wang, Yuhang Ding, Yunxiao Mai, Ruinan Li, Xinyu Shao, Wenlong Chen, Yiming Li, Luhaoxiang Liu, Haoran Wang, Kangkang Liu and 4 more

Erratum issuedAbstract read
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In one paragraph

Article in Frontiers in pharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
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

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors.

Xiaomin Wang *Department of Radiology, The Second Hospital of Tianjin Medical University, Tianjin Medical University, Tianjin, China.
Yuhang Ding *Department of Radiology, The Second Hospital of Tianjin Medical University, Tianjin Medical University, Tianjin, China.
Yunxiao Mai *Department of Radiology, The Second Hospital of Tianjin Medical University, Tianjin Medical University, Tianjin, China.
Ruinan LiDepartment of Radiology, The Second Hospital of Tianjin Medical University, Tianjin Medical University, Tianjin, China.
Xinyu ShaoNational Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
Wenlong ChenDepartment of Radiology, The Second Hospital of Tianjin Medical University, Tianjin Medical University, Tianjin, China.
Yiming LiDepartment of Radiology, The Second Hospital of Tianjin Medical University, Tianjin Medical University, Tianjin, China.
Luhaoxiang LiuDepartment of Radiology, The Second Hospital of Tianjin Medical University, Tianjin Medical University, Tianjin, China.
Haoran WangDepartment of Radiology, The Second Hospital of Tianjin Medical University, Tianjin Medical University, Tianjin, China.
Kangkang LiuTianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin Medical University, Tianjin, China.
Yuanjie NiuTianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin Medical University, Tianjin, China.
Jianmin LiTianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin Medical University, Tianjin, China.
Guoping XuDepartment of Radiology, The Second Hospital of Tianjin Medical University, Tianjin Medical University, Tianjin, China.
Yang ZhaoDepartment of Radiology, The Second Hospital of Tianjin Medical University, Tianjin Medical University, Tianjin, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Doxorubicin (DOX) resistance remains a major obstacle to effective chemotherapy in breast cancer. However, the pharmacologically actionable regulators sustaining this resistant phenotype and its therapeutic vulnerabilities remain incompletely defined. Methods: DOX-resistant breast cancer cell models were established and treated with the EZH2 inhibitors tazemetostat or GSK126, alone or in combination with DOX. Cell viability, oxidative stress, DNA damage, and mitochondrial function were assessed Results: EZH2 was highly expressed in breast cancer and correlated with poor clinical outcomes. DOX treatment induced adaptive upregulation of EZH2 in both sensitive and resistant cells. Pharmacological inhibition of EZH2 markedly restored DOX sensitivity and exhibited strong synergistic cytotoxicity in resistant models. EZH2 blockade enhanced DOX-induced oxidative stress and DNA damage, with concomitant suppression of multiple DNA repair pathways and increased γH2AX accumulation. Transcriptomic and functional analyses revealed disrupted mitochondrial function and energy metabolism, characterized by loss of mitochondrial membrane potential and ATP depletion. Conclusion: EZH2 is a critical determinant of DOX resistance in breast cancer by sustaining DNA damage tolerance and metabolic homeostasis. Pharmacological targeting of EZH2 in combination with DOX represents a rational strategy to overcome chemoresistance in breast cancer.

Indexed as

breast cancerDNA damagedoxorubicinEZH2metabolic vulnerabilityresistance

Identifiers

PMID42222149
PMCPMC13216663

What Socratic holds

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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 Socratic graph.