ArticleNeuro-oncology2020
HER2 antibody-drug conjugate controls growth of breast cancer brain metastases in hematogenous xenograft models, with heterogeneous blood-tumor barrier penetration unlinked to a passive marker.
Article in Neuro-oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 39 citations in OpenAlex.
- Preclinical evaluation of trastuzumab deruxtecan in a new HER2+ leptomeningeal colonization model.Cancer letters · 2026Article
- Engineered zwitterion-nanodelivery for precision targeting of brain metastases.Nature communications · 2026Article
- Impact of High Lymph Node Burden on Brain Metastases in Patients Who Achieved Pathological Complete Response after Neoadjuvant Chemotherapy in HER2-Positive Breast Cancer.Cancer research and treatment · 2026Article
- Trastuzumab deruxtecan efficacy, FcRn-facilitated penetration of the blood-tumor barrier, and distribution to tumor cells in HER2+ brain metastasis model systems.Neuro-oncology · 2026Article
- Bridging the blood-brain barrier: strategies to improve delivery of biologics to tumors in the brain.Fluids and barriers of the CNS · 2026Review
- Novel treatment strategies and key research priorities for patients with breast cancer and central nervous system (CNS) metastases.NPJ breast cancer · 2025Review
- Bridging molecular insights and clinical application: non-coding RNAs, targeted drug delivery, and metastatic breast cancer therapy.Discover oncology · 2025Review
- HIF-1 promotes murine breast cancer brain metastasis by increasing production of integrin β3-containing extracellular vesicles.The Journal of clinical investigation · 2025Article
- A new, immunocompetent brain-metastatic mouse model of HER2-positive breast cancer.Clinical & experimental metastasis · 2025Article
- Exposed Phosphatidylserine as a Biomarker for Clear Identification of Breast Cancer Brain Metastases in Mouse Models.Cancers · 2024Article
- Distinct uptake and elimination profiles for trastuzumab, human IgG, and biocytin-TMR in experimental HER2+ brain metastases of breast cancer.Neuro-oncology · 2024Article
- Article
- Gastric cancer with brain metastasis: from molecular characteristics and treatment.Frontiers in oncology · 2024Review
- A tissue-engineered model of the blood-tumor barrier during metastatic breast cancer.Fluids and barriers of the CNS · 2023Article
- Emerging therapeutics and evolving assessment criteria for intracranial metastases in patients with oncogene-driven non-small-cell lung cancer.Nature reviews. Clinical oncology · 2023Review
- Understanding the activity of antibody-drug conjugates in primary and secondary brain tumours.Nature reviews. Clinical oncology · 2023Review
- Review
- Comparison of Three Transcytotic Pathways for Distribution to Brain Metastases of Breast Cancer.Molecular cancer therapeutics · 2023Article
- Molecular landscape and emerging therapeutic strategies in breast cancer brain metastasis.Therapeutic advances in medical oncology · 2023Review
- The Extension of the LeiCNS-PK3.0 Model in Combination with the "Handshake" Approach to Understand Brain Tumor Pathophysiology.Pharmaceutical research · 2022Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundBrain metastases of HER2+ breast cancer persist as a clinical challenge. Many therapeutics directed at human epidermal growth factor receptor 2 (HER2) are antibodies or antibody-drug conjugates (ADCs), and their permeability through the blood-tumor barrier (BTB) is poorly understood. We investigated the efficacy of a biparatopic anti-HER2 antibody-tubulysin conjugate (bHER2-ATC) in preclinical models of brain metastases.
methodsThe compound was evaluated in 2 hematogenous HER2+ brain metastasis mouse models, SUM190-BR and JIMT-1-BR. Endpoints included metastasis count, compound brain penetration, cancer cell proliferation, and apoptosis.
resultsBiparatopic HER2-ATC 3 mg/kg prevented metastasis outgrowth in the JIMT-1-BR model. At 1 mg/kg bHER2-ATC, a 70% and 92% reduction in large and micrometastases was observed. For the SUM190-BR model, an 85% and 53% reduction, respectively, in large and micrometastases was observed at 3 mg/kg, without statistical significance. Proliferation was reduced in both models at the highest dose. At the endpoint, bHER2-ATC uptake covered a median of 4-6% and 7-17% of metastasis area in the JIMT-1-BR and SUM190-BR models, respectively. Maximal compound uptake in the models was 19% and 86% in JIMT-1-BR and SUM190-BR, respectively. Multiple lesions in both models demonstrated ADC uptake in the absence or low diffusion of Texas Red Dextran, a marker of paracellular permeability. Using in vitro BTB assays, the ADC was endocytosed into brain endothelial cells, identifying a potentially new mechanism of antibody permeability.
conclusionsBiparatopic HER2-ATC significantly prevented JIMT-1-BR brain metastasis outgrowth and showed activity in the SUM190-BR model. The bHER2-ATC penetration into metastases that are impermeable to fluorescent dye suggested an endocytic mechanism of brain penetration.
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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.