Evidence map›Paper›PMID 42185286›Full record

ArticleNature communications2026

An HDAC4-specific PROTAC degrader achieves radiation sensitization by enhancing ferroptosis in lung cancer.

Chun Cheng, Longhua Sun, Jiaxue Yang, Zhiliang Liu, Fan Zhang, Lingyan Qiu, Meng Yu, Ting Wang, Jianxin Huang, Li Wang and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

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.

Chun Cheng *Jiangxi Key Laboratory of Oncology, Department of Center Laboratory, The Third Affiliated Hospital of Nanchang University, Jiangxi Medical College, Nanchang University, Nanchang, China.ORCID http://orcid.org/0009-0000-2172-8111
Longhua Sun *Department of Respiratory, the First Affiliated Hospital of Nanchang University, Nanchang, China.
Jiaxue Yang *Jiangxi Key Laboratory of Oncology, Department of Center Laboratory, The Third Affiliated Hospital of Nanchang University, Jiangxi Medical College, Nanchang University, Nanchang, China.ORCID http://orcid.org/0000-0002-7217-3520
Zhiliang Liu *Department of Pathology, Jiangxi Cancer Hospital, Nanchang, China.
Fan Zhang *Jiangxi Key Laboratory of Oncology, Department of Center Laboratory, The Third Affiliated Hospital of Nanchang University, Jiangxi Medical College, Nanchang University, Nanchang, China.
Lingyan QiuJiangxi Key Laboratory of Oncology, Department of Center Laboratory, The Third Affiliated Hospital of Nanchang University, Jiangxi Medical College, Nanchang University, Nanchang, China.
Meng YuJiangxi Key Laboratory of Oncology, Department of Center Laboratory, The Third Affiliated Hospital of Nanchang University, Jiangxi Medical College, Nanchang University, Nanchang, China.
Ting WangJiangxi Key Laboratory of Oncology, Department of Center Laboratory, The Third Affiliated Hospital of Nanchang University, Jiangxi Medical College, Nanchang University, Nanchang, China.
Jianxin HuangDepartment of Respiratory, the First Affiliated Hospital of Nanchang University, Nanchang, China.
Li WangDepartment of Radiotherapy, Eye & ENT Hospital, Fudan University, Shanghai, China.
Wei-Ping MinDepartment of Surgery, Pathology and Oncology, University of Western Ontario, London, ON, Canada.
Tingxiu XiangChongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing, China. xiangtx@cqmu.edu.cn.ORCID http://orcid.org/0000-0003-4589-0599
Kaishun HuGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China. huksh3@mail.sysu.edu.cn.ORCID http://orcid.org/0000-0003-2157-6239
Yi SangJiangxi Key Laboratory of Oncology, Department of Center Laboratory, The Third Affiliated Hospital of Nanchang University, Jiangxi Medical College, Nanchang University, Nanchang, China. ndsfy001889@ncu.edu.cn.ORCID http://orcid.org/0000-0001-6534-0741

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Post-translational modifications (PTMs) play a critical role in cancer radioresistance, yet how they regulate ferroptosis to influence radiotherapy response remains poorly understood. Here, we show that HDAC4 promotes radiation resistance in lung cancer by inhibiting ferroptosis. Through a CRISPR screen in patient-derived organoids, we identify HDAC4 as a key mediator. Mechanistically, HDAC4 acts as an E3 SUMO ligase that SUMOylates MBD1, preventing its ubiquitination and degradation. Stabilized MBD1 represses TP53 and CYP1A1 transcription, thereby suppressing lipid reactive oxygen species formation and ferroptosis. To target HDAC4, we develop a proteolysis-targeting chimera (PROTAC), TP1, based on tasquinimod, which binds and degrades HDAC4 specifically, as confirmed by surface plasmon resonance and proteomics. TP1 exhibits stronger radiosensitizing effects than tasquinimod in lung cancer organoids and xenograft models. Our findings uncover HDAC4 as a suppressor of ferroptosis in radioresistance and present a PROTAC-based strategy to enhance radiotherapy efficacy.

Indexed as

FerroptosisHistone DeacetylasesLung NeoplasmsRadiation-Sensitizing AgentsRadiation ToleranceAnimalsCell Line, TumorDNA-Binding ProteinsHumansMiceOrganoidsProteolysisProteolysis Targeting ChimeraRepressor ProteinsUbiquitinationXenograft Model Antitumor AssaysDNA-Binding ProteinsHDAC4 protein, humanHistone DeacetylasesProteolysis Targeting ChimeraRadiation-Sensitizing AgentsRepressor Proteins

Identifiers

PMID42185286
PMCPMC13389272

What OpenQuestion 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 OpenQuestion graph.