ArticleNature cancer2025
p95HER2, a truncated form of the HER2 oncoprotein, drives an immunosuppressive program in HER2
Article in Nature cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it.
- CDK4/6 inhibitors as conditional immune-priming agents in breast cancer: therapeutic windows, sequencing strategies, and rational combinations with immunotherapy, radiotherapy, and antibody-drug conjugates.Frontiers in immunology · 2026Pooled it
- The immunology of human breast cancer.Nature reviews. Immunology · 2026Review
- AKAP13 regulates GLI1/ULK1 axis and drive tumor resistance to next-generation HER2-targeted therapies.Oncogene · 2026Article
- HER2 targeted therapy resistance in breast cancer: from molecular landscape to clinical aspects.Science China. Life sciences · 2026Review
- Mechanical unloading promotes adult cardiomyocyte proliferation through epicardial NRG1-ERBB4 signaling.Nature cardiovascular research · 2026Article
- P95-HER2 promotes metastatic progression by biasing MRTFA dependent signaling.bioRxiv : the preprint server for biology · 2026Article
- Bispecific antibody AP402 targets p95HER2 and induces costimulation through CD137 to improve efficacy for HER2-positive tumors.Molecular medicine (Cambridge, Mass.) · 2026Article
- Clinical Outcomes for Patients who Received Both Trastuzumab Deruxtecan (T-DXd) and Trastuzumab Emtansine (T-DM1) for HER2-Mutant non-Small Cell Lung Cancer.JTO clinical and research reports · 2026Article
- The impact of the PI3K/AKT/mTOR signaling pathway on trastuzumab resistance in HER2-positive gastric cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- A degrader of HER2 and EGFR abolishes p95HER2 and shows robust antitumor efficacy in HER2-positive breast cancer.Scientific reports · 2026Article
- Trastuzumab deruxtecan in the treatment of HER2-positive gastric cancer: a comprehensive review.Future oncology (London, England) · 2025Review
- Therapeutic challenges in HER2-targeted antibody therapies: trastuzumab and its ADC derivatives in breast cancer.American journal of cancer research · 2025Review
Corrections and comments
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Authors and funding
35 authors.
Funding
Abstract
Resistance to human epidermal growth factor receptor 2 (HER2)-targeted therapies and immuno-oncology agents poses a major challenge in treating HER2-positive breast cancer. Here we demonstrate that p95HER2, a truncated form of HER2, drives immune evasion in HER2-positive female breast cancer, enhancing tumor growth and conferring therapy resistance. This stems from the unique ability of p95HER2 to promote cancer cell-intrinsic programmed death ligand 1 expression and secretion of immunosuppressive mediators including interleukin 6. In preclinical models, this impairs the efficacy of trastuzumab deruxtecan, a HER2-directed antibody-drug conjugate (ADC) that relies on immunogenic responses to cell death for full efficacy. Importantly, we find that neratinib potently directs proteasomal degradation of p95HER2, relieving its immunosuppressive effects, and provide proof of concept that neratinib and/or agents targeting p95HER2 downstream mediators can restore antitumor immunity and trastuzumab deruxtecan efficacy. This study reveals a p95HER2-specific therapy resistance mechanism in HER2-positive female breast cancer and highlights the potential value of targeting p95HER2 to improve outcomes with ADCs or immuno-oncology agents.
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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.