ArticleNature communications2025
ZMYND8 drives HER2 antibody resistance in breast cancer via lipid control of IL-27.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 8 papers.
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
8 citing papers in PubMed.
- STARD10 promotes progression of HER2+ breast cancer and intracellular lipid metabolism via the cAMP/PKA/CREB1 signaling axis.Cancer biology & therapy · 2026Article
- Sterol regulatory element‑binding proteins: Master regulators of lipid metabolic reprogramming in cancer and emerging therapeutic targets (Review).Oncology reports · 2026Review
- The chromatin reader ZMYND8 recruits the NuRD component GATAD2A through its MYND domain to regulate MAPT213 long noncoding RNA transcription.The Journal of biological chemistry · 2026Article
- Article
- Review
- Linoleic acid metabolic reprogramming is linked to immunometabolic remodeling and post-transplant recurrence risk in hepatocellular carcinoma.Frontiers in immunology · 2026Article
- Targeting the tripartite axis of immune-metabolic-spatial crosstalk to overcome therapy resistance in breast cancer.Frontiers in immunology · 2026Review
- Article
Corrections and comments
- Erratum issued
Authors and funding
14 authors.
Funding
Abstract
Anti-HER2 antibodies are effective but often lead to resistance in patients with HER2+ breast cancer. Here, we report an epigenetic crosstalk with aberrant glycerophospholipid metabolism and inflammation as a key resistance mechanism of anti-HER2 therapies in HER2+ breast cancer. Histone reader ZMYND8 specifically confers resistance to cancer cells against trastuzumab and/or pertuzumab. Mechanistically, ZMYND8 enhances cPLA2α expression in resistant tumor cells through inducing c-Myc. cPLA2α inactivates phosphatidylcholine-specific phospholipase C to inhibit phosphatidylcholine breakdown into diacylglycerol, which diminishes protein kinase C activity leading to interleukin-27 secretion. Supplementation with interleukin-27 protein counteracts cPLA2α loss to reinforce trastuzumab resistance in HER2+ tumor cells and patient-derived organoids. Upregulation of ZMYND8, c-Myc, cPLA2α, and IL-27 is prevalent in HER2+ breast cancer patients following HER2-targeted therapies. Targeting c-Myc or cPLA2α effectively overcomes anti-HER2 therapy resistance in patient-derived xenografts. Collectively, this study uncovers a druggable signaling cascade that drives resistance to HER2-targeted therapies in HER2+ breast cancer.
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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.