Evidence map›Paper›PMID 40652527›Full record

ArticleThe FEBS journal2025

Overcoming BET-inhibitor JQ1 resistance in aggressive non-small cell lung cancer by inducing ferroptosis via inhibition of the BRD2-FTH1 axis.

Stefania Scicchitano, Cinzia Garofalo, Beatrice Stella, Gianluca Santamaria, Flora Cozzolino, Vittoria Monaco, Flavia Biamonte, Maria Monti, Eleonora Vecchio, Maria Concetta Faniello

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In one paragraph

Article in The FEBS journal, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

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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

4 citing papers in PubMed.

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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

10 authors.

Stefania ScicchitanoDepartment of Experimental and Clinical Medicine, Magna Graecia University of Catanzaro, Italy.
Cinzia GarofaloDepartment of Experimental and Clinical Medicine, Magna Graecia University of Catanzaro, Italy.
Beatrice StellaDepartment of Experimental and Clinical Medicine, Magna Graecia University of Catanzaro, Italy.
Gianluca SantamariaDepartment of Experimental and Clinical Medicine, Magna Graecia University of Catanzaro, Italy.
Flora CozzolinoDepartment of Chemical Sciences, Federico II University of Naples and CEINGE Advanced Biotechnologies Franco Salvatore, Italy.
Vittoria MonacoDepartment of Chemical Sciences, Federico II University of Naples and CEINGE Advanced Biotechnologies Franco Salvatore, Italy.
Flavia BiamonteDepartment of Experimental and Clinical Medicine, Magna Graecia University of Catanzaro, Italy.
Maria MontiDepartment of Chemical Sciences, Federico II University of Naples and CEINGE Advanced Biotechnologies Franco Salvatore, Italy.
Eleonora VecchioDepartment of Experimental and Clinical Medicine, Magna Graecia University of Catanzaro, Italy.ORCID https://orcid.org/0000-0001-8422-2679
Maria Concetta FanielloDepartment of Experimental and Clinical Medicine, Magna Graecia University of Catanzaro, Italy.ORCID https://orcid.org/0000-0001-6938-2754

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Recent studies emphasize the involvement of the nuclear H ferritin subunit (FTH1; also known as ferritin heavy chain) in DNA protection from oxidative damage and transcriptional regulation. Bromodomain and extra-terminal domain (BET) proteins act as epigenome readers for transcriptional regulation. Among them, the role of bromodomain-containing protein 2 (BRD2) in non-small cell lung carcinoma (NSCLC) remains unclear. Moreover, the clinical utilization of BET bromodomain inhibition is severely limited by different sensitivities among NSCLC subtypes. This study provides the first evidence of nuclear BRD2-FTH1 functional interplay. Nuclear FTH1 is associated with BRD2, not bromodomain-containing protein 4 (BRD4), in a panel of NSCLC cell lines and affects BRD2 protein stability only in more aggressive types of NSCLC cells. In addition, the protective function of FTH1 was abrogated in FTH1-silenced cells that are resistant to synthetic BET bromodomain inhibitor JQ1 (a thieno-triazolo-1,4-diazepine) but not in JQ1-sensitive cells, leading to an increase in mortality. Then, the potential mechanism by which the combination of JQ1 with FTH1 silencing induces cell death was explored. The results show that ferroptosis is involved in the anticancer effect of JQ1 upon FTH1 silencing only in JQ1-insensitive cells. Moreover, the expression of ferroptosis-associated genes glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11) and solute carrier family 3 member 2 (SLC3A2) was downregulated under JQ1 treatment only after FTH1 silencing, indicating that the BRD2 inhibition due to the co-treatment could regulate the expression of ferroptosis-associated genes. In summary, for the first time, our data suggest that FTH1 silencing may serve as an effective anti-tumor strategy to enhance the activity of JQ1, acting to overcome the chemotherapy resistance in more aggressive NSCLCs.

Indexed as

AzepinesCarcinoma, Non-Small-Cell LungDrug Resistance, NeoplasmFerroptosisLung NeoplasmsProtein Serine-Threonine KinasesTriazolesBromodomain Containing ProteinsCell Line, TumorFerritinsGene Expression Regulation, NeoplasticHumansOxidoreductasesTranscription FactorsAzepinesBRD2 protein, humanBromodomain Containing ProteinsFerritinsFTH1 protein, human(+)-JQ1 compoundOxidoreductasesProtein Serine-Threonine KinasesTranscription FactorsTriazolesBRD2ferroptosisFTH1JQ1lung canceroxidative damage

Identifiers

PMID40652527
PMCPMC12699187

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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.