ArticleJCI insight2021
The impact of tumor epithelial and microenvironmental heterogeneity on treatment responses in HER2+ breast cancer.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- Radiomic Analysis of MRI for Assessing Response to Neoadjuvant Chemoradiotherapy in Rectal Adenocarcinoma: A Systematic Review and Metaanalysis.Molecular imagingPooled it
- The immunology of human breast cancer.Nature reviews. Immunology · 2026Review
- HER2 Heterogeneous Breast Cancer Models Reveal Novel Therapeutic Targets and Subclonal Dynamics during Evolution to Resistance to HER2-Targeted Therapies.Cancer discovery · 2026Article
- Characterization of HER2-Positive Murine Breast Cancer Models for Investigating HER2-Targeted Therapy and Immunotherapy.Cancers · 2026Article
- Multiparametric MRI-based radiomics of whole-tumor and habitat regions for predicting HER2 status in young breast cancer: a two-center study.Frontiers in oncology · 2026Article
- Macrophage-Mediated Cellular Communication Networks in Lung Squamous Cell Carcinoma and Adenocarcinoma Revealed by Single-Cell Sequencing.Mediators of inflammation · 2026Article
- Decoding breast cancer: insights into molecular pathways & therapeutic approaches.Discover oncology · 2025Review
- Cell sorting based on single nucleotide variation enables characterization of mutation-dependent transcriptome and chromatin states.Nucleic acids research · 2025Article
- MRI-based quantification of intratumoral heterogeneity for intrahepatic mass-forming cholangiocarcinoma grading: a multicenter study.Insights into imaging · 2025Article
- An Optimized Protocol for Simultaneous Propagation of Patient-derived Organoids and Matching CAFs.Bio-protocol · 2025Article
- Highly multiplexed imaging reveals prognostic immune and stromal spatial biomarkers in breast cancer.JCI insight · 2025Article
- From Images to Genes: Radiogenomics Based on Artificial Intelligence to Achieve Non-Invasive Precision Medicine in Cancer Patients.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Analysis of single-cell and spatial transcriptomics in TNBC cell-cell interactions.Frontiers in immunology · 2025Review
- The Biological Roles and Clinical Applications of the PI3K/AKT Pathway in Targeted Therapy Resistance in HER2-Positive Breast Cancer: A Comprehensive Review.International journal of molecular sciences · 2024Review
- Advancing precision cancer immunotherapy drug development, administration, and response prediction with AI-enabled Raman spectroscopy.Frontiers in immunology · 2024Review
- The HSP90 inhibitor HVH-2930 exhibits potent efficacy against trastuzumab-resistant HER2-positive breast cancer.Theranostics · 2024Article
- A convolutional neural network STIFMap reveals associations between stromal stiffness and EMT in breast cancer.Nature communications · 2023Article
- Single-cell heterogeneity of EGFR and CDK4 co-amplification is linked to immune infiltration in glioblastoma.Cell reports · 2023Article
- Phenotypic deconvolution in heterogeneous cancer cell populations using drug-screening data.Cell reports methods · 2023Article
- Targeting HER2-positive breast cancer: advances and future directions.Nature reviews. Drug discovery · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
23 authors at 8 institutions in 3 countries.
Funding
Abstract
Despite the availability of multiple human epidermal growth factor receptor 2-targeted (HER2-targeted) treatments, therapeutic resistance in HER2+ breast cancer remains a clinical challenge. Intratumor heterogeneity for HER2 and resistance-conferring mutations in the PIK3CA gene (encoding PI3K catalytic subunit α) have been investigated in response and resistance to HER2-targeting agents, while the role of divergent cellular phenotypes and tumor epithelial-stromal cell interactions is less well understood. Here, we assessed the effect of intratumor cellular genetic heterogeneity for ERBB2 (encoding HER2) copy number and PIK3CA mutation on different types of neoadjuvant HER2-targeting therapies and clinical outcome in HER2+ breast cancer. We found that the frequency of cells lacking HER2 was a better predictor of response to HER2-targeted treatment than intratumor heterogeneity. We also compared the efficacy of different therapies in the same tumor using patient-derived xenograft models of heterogeneous HER2+ breast cancer and single-cell approaches. Stromal determinants were better predictors of response than tumor epithelial cells, and we identified alveolar epithelial and fibroblastic reticular cells as well as lymphatic vessel endothelial hyaluronan receptor 1-positive (Lyve1+) macrophages as putative drivers of therapeutic resistance. Our results demonstrate that both preexisting and acquired resistance to HER2-targeting agents involve multiple mechanisms including the tumor microenvironment. Furthermore, our data suggest that intratumor heterogeneity for HER2 should be incorporated into treatment design.
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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.