ArticleCell death & disease2025
Small molecule-mediated inhibition of the oxidoreductase ERO1A restrains aggressive breast cancer by impairing VEGF and PD-L1 in the tumor microenvironment.
Article in Cell death & disease, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled 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.
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.
Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it.
- ERO1α as a Potential Drug Target for Breast Cancer: A Systematic Review of Current Evidence.International journal of molecular sciences · 2025Pooled it
- ER proteostasis meets mitochondrial function: contact sites as hubs of communication and therapeutic targets.The FEBS journal · 2026Review
- Remodelling the tumour microenvironment and beyond: ERO1A as a multifaceted regulator and emerging therapeutic target in cancer.Clinical and translational medicine · 2026Review
- ERO1a fosters glioblastoma aggressiveness and metabolic flexibility by regulating mitochondria-associated membrane dynamics.Nature cell biology · 2026Article
- Discovery of a pyrazolopyridine alkaloid that mitigates neuronal ER stress and age-related decline.Communications biology · 2026Article
- Targeting the Endoplasmic Reticulum Oxidoreductin-1 Alpha-Protein Disulfide Isomerase Redox Interface as a Therapeutic Strategy in Cancer.Biomedicines · 2026Review
- Article
- ERO1A promotes the proliferation, migration and invasion of bladder cancer through ALOX5 mediated activation of JAK-STAT signaling pathway.Journal of translational medicine · 2025Article
- Pyrazolone-based ERO1 inhibitors in ERO1-driven triple-negative breast cancer and SEPN1-related myopathy: Structure-activity relationship and therapeutic potential.Pharmacological research · 2025Article
- Prognostic implication of endoplasmic reticulum stress-related gene signature in lung adenocarcinoma and its effect on tumor immunity.Translational cancer research · 2025Article
- Endoplasmic reticulum oxidoreductin 1α as a potential therapeutic target in diseases: from oxidative protein folding to pathophysiological mechanisms.Frontiers in pharmacology · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
26 authors.
Funding
Abstract
Cancer cells adapt to harsh environmental conditions by inducing the Unfolded Protein Response (UPR), of which ERO1A is a mediator. ERO1A aids protein folding by acting as a protein disulfide oxidase, and under cancer-related hypoxia conditions, it favors the folding of angiogenic VEGFA, leading tumor cells to thrive and spread. The upregulation of ERO1A in cancer cells, oppositely to the dispensability of ERO1A activity in healthy cells, renders ERO1A a perfect target for cancer therapy. Here, we report the upregulation of ERO1A in a cohort of aggressive triple-negative breast cancer (TNBC) patients in which ERO1A levels correlate with a higher risk of breast tumor recurrence and metastatic spread. For ERO1A target validation and therapy in TNBC, we designed new ERO1A inhibitors in a structure-activity campaign of the prototype EN460. Cell-based screenings showed that the presence of the Micheal acceptor in the compound is necessary to engage the cysteine 397 of ERO1A but not sufficient to set out the inhibitory effect on ERO1A. Indeed, the ERO1 inhibitor must adopt a non-coplanar rearrangement within the ERO1A binding site. I2 and I3, two new EN460 analogs with different phenyl-substituted moieties, efficiently inhibited ERO1A, blunting VEGFA secretion. Accordingly, in vitro assays to measure ERO1A engagement and inhibition confirmed that I2 and I3 bind ERO1A and restrain its activity with a IC50 in a low micromolar range. EN460, I2 and I3 triggered breast cancer cytotoxicity while specifically inhibiting ERO1A in a dose-dependent manner. I2 more efficiently impaired cancer-relevant features such as VEGFA secretion and related cell migration. I2 also acted on the tumor microenvironment and viability of xenografts and syngeneic TNBC. Thus, small molecule-mediated ERO1A pharmacological inhibition is feasible and promises to lead to effective therapy for the still incurable TNBC.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.