ArticleOncotarget2016
HER2-HER3 dimer quantification by FLIM-FRET predicts breast cancer metastatic relapse independently of HER2 IHC status.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 37 citations in OpenAlex.
- Partitioning of the truncated insulin receptor DAF-2B between homodimers and heterodimers influences insulin signaling in C. elegans.PLoS genetics · 2026Article
- Recent Progress in Exosome-Derived Nanocarriers for Breast Cancer Therapy: Advances, Translational Barriers, and Scale-Up Considerations.Pharmaceutical research · 2026Review
- Pertuzumab Enhances the Antitumor Activity of T-DXd in HER2-Positive Gastric Cancer Cells.Molecular cancer therapeutics · 2026Article
- Dual-targeting and steric hindrance resolution in HER2 IHC: a novel approach to improve diagnostic sensitivity.BMC cancer · 2025Article
- Single-molecule localization microscopy as a tool to quantify di/oligomerization of receptor tyrosine kinases and G protein-coupled receptors.Molecular pharmacology · 2025Review
- The Brain-Penetrant Pan-ErbB Inhibitor Poziotinib Effectively Targets HER2+ Breast Cancer Brain Metastases.Cancer research · 2025Article
- HER4 is a high-affinity dimerization partner for all EGFR/HER/ErbB family proteins.Protein science : a publication of the Protein Society · 2024Article
- Patritumab deruxtecan in HER2-negative breast cancer: part B results of the window-of-opportunity SOLTI-1805 TOT-HER3 trial and biological determinants of early response.Nature communications · 2024Article
- Overcoming brain-derived therapeutic resistance in HER2+ breast cancer brain metastasis.bioRxiv : the preprint server for biology · 2024Article
- Using quantitative single molecule localization microscopy to optimize multivalent HER2-targeting ligands.Frontiers in medicine · 2023Article
- Molecular Assessment of HER2 to Identify Signatures Associated with Therapy Response in HER2-Positive Breast Cancer.Cancers · 2022Article
- Article
- Extensive conformational and physical plasticity protects HER2-HER3 tumorigenic signaling.Cell reports · 2022Article
- FLIM as a Promising Tool for Cancer Diagnosis and Treatment Monitoring.Nano-micro letters · 2021Review
- A DNA-nanoassembly-based approach to map membrane protein nanoenvironments.Nature nanotechnology · 2021Article
- EGFR Expression in HER2-Driven Breast Cancer Cells.International journal of molecular sciences · 2020Article
- HER2-HER3 Heterodimer Quantification by FRET-FLIM and Patient Subclass Analysis of the COIN Colorectal Trial.Journal of the National Cancer Institute · 2020Article
- Article
- Fast single-cell biochemistry: theory, open source microscopy and applications.Methods and applications in fluorescence · 2019Article
- Automated Fluorescence Lifetime Imaging High-Content Analysis of Förster Resonance Energy Transfer between Endogenously Labeled Kinetochore Proteins in Live Budding Yeast Cells.SLAS technology · 2019Article
Corrections and comments
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Authors and funding
16 authors at 7 institutions in 3 countries.
Funding
Abstract
Overexpression of HER2 is an important prognostic marker, and the only predictive biomarker of response to HER2-targeted therapies in invasive breast cancer. HER2-HER3 dimer has been shown to drive proliferation and tumor progression, and targeting of this dimer with pertuzumab alongside chemotherapy and trastuzumab, has shown significant clinical utility. The purpose of this study was to accurately quantify HER2-HER3 dimerisation in formalin fixed paraffin embedded (FFPE) breast cancer tissue as a novel prognostic biomarker.FFPE tissues were obtained from patients included in the METABRIC (Molecular Taxonomy of Breast Cancer International Consortium) study. HER2-HER3 dimerisation was quantified using an improved fluorescence lifetime imaging microscopy (FLIM) histology-based analysis. Analysis of 131 tissue microarray cores demonstrated that the extent of HER2-HER3 dimer formation as measured by Förster Resonance Energy Transfer (FRET) determined through FLIM predicts the likelihood of metastatic relapse up to 10 years after surgery (hazard ratio 3.91 (1.61-9.5), p = 0.003) independently of HER2 expression, in a multivariate model. Interestingly there was no correlation between the level of HER2 protein expressed and HER2-HER3 heterodimer formation. We used a mathematical model that takes into account the complex interactions in a network of all four HER proteins to explain this counterintuitive finding.Future utility of this technique may highlight a group of patients who do not overexpress HER2 protein but are nevertheless dependent on the HER2-HER3 heterodimer as driver of proliferation. This assay could, if validated in a group of patients treated with, for instance pertuzumab, be used as a predictive biomarker to predict for response to such targeted therapies.
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Registered trials
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