ArticleProceedings of the National Academy of Sciences of the United States of America2024
Cancer-stromal cell interactions in breast cancer brain metastases induce glycocalyx-mediated resistance to HER2-targeting therapies.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. 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 19 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
19 citing papers in PubMed.
- Intratumoral desmoplastic stroma in carcinoma brain metastases harbors stromal cells with a cancer-associated fibroblast (CAF)-like immunophenotype.Virchows Archiv : an international journal of pathology · 2026Article
- HER2 targeted therapy resistance in breast cancer: from molecular landscape to clinical aspects.Science China. Life sciences · 2026Review
- The microenvironment dictates glyco-immune surveillance via HSF1-mediated metabolism.Science advances · 2026Article
- Incorporation of Novel Synthetic Glycolipids in Liposomal Nanoparticles Affects Opsonization and In Vivo Clearance.Angewandte Chemie (International ed. in English) · 2026Article
- Future directions in the treatment of brain metastases: evaluating the role of cellular players in the tumour microenvironment.Acta neuropathologica · 2026Review
- Unbiased recording and identification of thymic cellular interactomes using synthetic Notch receptors.Nature communications · 2026Article
- Targeting one-carbon metabolic vulnerabilities of metastasis with therapeutic potential.bioRxiv : the preprint server for biology · 2026Article
- Crosstalk in the brain tumor microenvironment: mechanisms, therapeutic strategies, and clinical advances.Military Medical Research · 2026Review
- Stealth missiles with precision guidance: A novel multifunctional nano-drug delivery system based on biomimetic cell membrane coating technology.Materials today. Bio · 2025Review
- The Tumour Glyco-Code: Sialylation as a Mediator of Stromal Cell Immunosuppression in the Tumour Microenvironment.European journal of immunology · 2025Review
- HDAC7 promotes renal cancer progression by reprogramming branched-chain amino acid metabolism.Science advances · 2025Article
- Anti‑HER2‑targeted therapies for the treatment of advanced HER2‑positive breast cancer with brain metastases (Review).Molecular and clinical oncology · 2025Review
- SNX10 deficiency impairs sensitivity to anti-HER2 antibody-drug conjugates via altering HER2 trafficking in HER2-positive breast cancer.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Mucin 5AC Promotes Breast Cancer Brain Metastasis through cMET/CD44v6.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Exosomes: a double-edged sword in cancer immunotherapy.MedComm · 2025Review
- Review
- Exploring New Frontiers: Alternative Breast Cancer Treatments Through Glycocalyx Research.The breast journal · 2025Review
- Mucins as Precision Biomarkers in Glioma: Emerging Evidence for Their Potential in Biospecimen Analysis and Outcome Prediction.Biomedicines · 2024Review
- Cancer-stromal cell interactions in breast cancer brain metastases induce glycocalyx-mediated resistance to HER2-targeting therapies.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
Corrections and comments
- Erratum issued
Authors and funding
19 authors.
Funding
Abstract
Brain metastatic breast cancer is particularly lethal largely due to therapeutic resistance. Almost half of the patients with metastatic HER2-positive breast cancer develop brain metastases, representing a major clinical challenge. We previously described that cancer-associated fibroblasts are an important source of resistance in primary tumors. Here, we report that breast cancer brain metastasis stromal cell interactions in 3D cocultures induce therapeutic resistance to HER2-targeting agents, particularly to the small molecule inhibitor of HER2/EGFR neratinib. We investigated the underlying mechanisms using a synthetic Notch reporter system enabling the sorting of cancer cells that directly interact with stromal cells. We identified mucins and bulky glycoprotein synthesis as top-up-regulated genes and pathways by comparing the gene expression and chromatin profiles of stroma-contact and no-contact cancer cells before and after neratinib treatment. Glycoprotein gene signatures were also enriched in human brain metastases compared to primary tumors. We confirmed increased glycocalyx surrounding cocultures by immunofluorescence and showed that mucinase treatment increased sensitivity to neratinib by enabling a more efficient inhibition of EGFR/HER2 signaling in cancer cells. Overexpression of truncated MUC1 lacking the intracellular domain as a model of increased glycocalyx-induced resistance to neratinib both in cell culture and in experimental brain metastases in immunodeficient mice. Our results highlight the importance of glycoproteins as a resistance mechanism to HER2-targeting therapies in breast cancer brain metastases.
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.