ArticleClinical cancer research : an official journal of the American Association for Cancer Research2010
A proteasome inhibitor, bortezomib, inhibits breast cancer growth and reduces osteolysis by downregulating metastatic genes.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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37 citing papers in PubMed, 65 citations in OpenAlex.
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- Using Deep Learning Models of Gene Regulation to Guide Drug Prioritization.bioRxiv : the preprint server for biology · 2026Article
- Reflections and perspectives on epigenetically mediated biological control: compromises in cancer and skeletal pathology.Academia biology · 2025Article
- An essential gene signature of breast cancer metastasis reveals targetable pathways.Breast cancer research : BCR · 2024Article
- Cytotoxicity of bismuth(III) dithiocarbamate derivatives by promoting a mitochondrial-dependent apoptotic pathway and suppressing MCF-7 breast adenocarcinoma cell invasion.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2024Article
- Overexpression of VIRMA confers vulnerability to breast cancers via the mCellular and molecular life sciences : CMLS · 2023Article
- The anti-tumor effect of proteasome inhibitor MG132 for human adenoid cystic carcinoma: correlate with the emerging role of Nrf2/Keap1 signaling pathway.Head & face medicine · 2022Article
- Review
- Production of Epoxyketone Peptide-Based Proteasome Inhibitors byFrontiers in microbiology · 2022Article
- Research progress of bone metastases: From disease recognition to clinical practice.Frontiers in oncology · 2022Review
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- ECMarker: interpretable machine learning model identifies gene expression biomarkers predicting clinical outcomes and reveals molecular mechanisms of human disease in early stages.Bioinformatics (Oxford, England) · 2021Article
- The proteostasis guardian HSF1 directs the transcription of its paralog and interactor HSF2 during proteasome dysfunction.Cellular and molecular life sciences : CMLS · 2021Article
- Review
- Role of the bone microenvironment in bone metastasis of malignant tumors - therapeutic implications.Cellular oncology (Dordrecht, Netherlands) · 2020Review
- Deubiquitinase PSMD7 regulates cell fate and is associated with disease progression in breast cancer.American journal of translational research · 2020Article
- Inhibition of the PI3K/AKT signaling pathway sensitizes diffuse large B-cell lymphoma cells to treatment with proteasome inhibitors via suppression of BAG3.Oncology letters · 2019Article
- Synergistic Effects of Bortezomib-OV Therapy and Anti-Invasive Strategies in Glioblastoma: A Mathematical Model.Cancers · 2019Article
- A perspective on malignancy in the marrow.Journal of cellular physiology · 2017Review
- The role of osteoblasts in bone metastasis.Journal of bone oncology · 2016Article
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
purposeThe incidence of bone metastasis in advanced breast cancer (BrCa) exceeds 70%. Bortezomib, a proteasome inhibitor used for the treatment of multiple myeloma, also promotes bone formation. We tested the hypothesis that proteasome inhibitors can ameliorate BrCa osteolytic disease. EXPERIMENTAL
designTo address the potentially beneficial effect of bortezomib in reducing tumor growth in the skeleton and counteracting bone osteolysis, human MDA-MB-231 BrCa cells were injected into the tibia of mice to model bone tumor growth for in vivo assessment of treatment regimens before and after tumor growth.
resultsControls exhibited tumor growth, destroying trabecular and cortical bone and invading muscle. Bortezomib treatment initiated following inoculation of tumor cells strikingly reduced tumor growth, restricted tumor cells mainly to the marrow cavity, and almost completely inhibited osteolysis in the bone microenvironment over a 3- to 4-week period as shown by [(18)F]fluorodeoxyglucose positron emission tomography, micro-computed tomography scanning, radiography, and histology. Thus, proteasome inhibition is effective in killing tumor cells within the bone. Pretreatment with bortezomib for 3 weeks before inoculation of tumor cells was also effective in reducing osteolysis. Our in vitro and in vivo studies indicate that mechanisms by which bortezomib inhibits tumor growth and reduces osteolysis result from inhibited cell proliferation, necrosis, and decreased expression of factors that promote BrCa tumor progression in bone.
conclusionThese findings provide a basis for a novel strategy to treat patients with BrCa osteolytic lesions, and represent an approach for protecting the entire skeleton from metastatic bone disease.
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