ArticleClinical cancer research : an official journal of the American Association for Cancer Research2014
Profound prevention of experimental brain metastases of breast cancer by temozolomide in an MGMT-dependent manner.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 65 citations in OpenAlex.
- Article
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- Drug treatment of breast cancer brain metastases: progress and challenges.Discover oncology · 2025Review
- Metastatic organotropism in small cell lung cancer.bioRxiv : the preprint server for biology · 2025Article
- Prevention of Brain Metastases: A New Frontier.Cancers · 2024Review
- Navigating breast cancer brain metastasis: Risk factors, prognostic indicators, and treatment perspectives.World journal of clinical oncology · 2024Article
- Leveraging translational insights toward precision medicine approaches for brain metastases.Nature cancer · 2023Review
- Breast cancer brain metastasis: from etiology to state-of-the-art modeling.Journal of biological engineering · 2023Review
- Comparison of Three Transcytotic Pathways for Distribution to Brain Metastases of Breast Cancer.Molecular cancer therapeutics · 2023Article
- Phase I Study and Cell-Free DNA Analysis of T-DM1 and Metronomic Temozolomide for Secondary Prevention of HER2-Positive Breast Cancer Brain Metastases.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Sabizabulin, a Potent Orally Bioavailable Colchicine Binding Site Agent, Suppresses HER2+ Breast Cancer and Metastasis.Cancers · 2022Article
- Homogeneity of antibody-drug conjugates critically impacts the therapeutic efficacy in brain tumors.Cell reports · 2022Article
- HER2-positive breast cancer brain metastasis: A new and exciting landscape.Cancer reports (Hoboken, N.J.) · 2022Review
- Preclinical Models of Brain Metastases in Breast Cancer.Biomedicines · 2022Review
- The PI3K/Akt/mTOR pathway as a preventive target in melanoma brain metastasis.Neuro-oncology · 2022Article
- The blood-tumour barrier in cancer biology and therapy.Nature reviews. Clinical oncology · 2021Review
- Animal models of brain metastasis.Neuro-oncology advances · 2021Article
- Inter-Metastatic Heterogeneity of Tumor Marker Expression and Microenvironment Architecture in a Preclinical Cancer Model.International journal of molecular sciences · 2021Article
- The In Vivo Selection Method in Breast Cancer Metastasis.International journal of molecular sciences · 2021Review
- Modeling Brain Metastasis Via Tail-Vein Injection of Inflammatory Breast Cancer Cells.Journal of visualized experiments : JoVE · 2021Article
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
purposeBrain metastases of breast cancer cause neurocognitive damage and are incurable. We evaluated a role for temozolomide in the prevention of brain metastases of breast cancer in experimental brain metastasis models. EXPERIMENTAL
designTemozolomide was administered in mice following earlier injection of brain-tropic HER2-positive JIMT-1-BR3 and triple-negative 231-BR-EGFP sublines, the latter with and without expression of O(6)-methylguanine-DNA methyltransferase (MGMT). In addition, the percentage of MGMT-positive tumor cells in 62 patient-matched sets of breast cancer primary tumors and resected brain metastases was determined immunohistochemically.
resultsTemozolomide, when dosed at 50, 25, 10, or 5 mg/kg, 5 days per week, beginning 3 days after inoculation, completely prevented the formation of experimental brain metastases from MGMT-negative 231-BR-EGFP cells. At a 1 mg/kg dose, temozolomide prevented 68% of large brain metastases, and was ineffective at a dose of 0.5 mg/kg. When the 50 mg/kg dose was administered beginning on days 18 or 24, temozolomide efficacy was reduced or absent. Temozolomide was ineffective at preventing brain metastases in MGMT-transduced 231-BR-EGFP and MGMT-expressing JIMT-1-BR3 sublines. In 62 patient-matched sets of primary breast tumors and resected brain metastases, 43.5% of the specimens had concordant low MGMT expression, whereas in another 14.5% of sets high MGMT staining in the primary tumor corresponded with low staining in the brain metastasis.
conclusionsTemozolomide profoundly prevented the outgrowth of experimental brain metastases of breast cancer in an MGMT-dependent manner. These data provide compelling rationale for investigating the preventive efficacy of temozolomide in a clinical setting.
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