ArticleOncotarget2017
Inflammatory breast cancer tumor emboli express high levels of anti-apoptotic proteins: use of a quantitative high content and high-throughput 3D IBC spheroid assay to identify targeting strategies.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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30 citing papers in PubMed, 46 citations in OpenAlex.
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- 3D Engineered Biomimetic Platform for Characterization of Collective Invasion, Tumor Emboli Formation, and Lymphatic Dissemination.IEEE open journal of engineering in medicine and biology · 2026Article
- Synthesis and Biological Evaluation of Herceptin-Conjugated Liposomes Loaded with Lipocalin-2 siRNA for the Treatment of Inflammatory Breast Cancer.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Treatment Response, Tumor Infiltrating Lymphocytes and Clinical Outcomes in Inflammatory Breast Cancer-Treated with Neoadjuvant Systemic Therapy.Cancer research communications · 2024Article
- Identification of barriers at the primary care provider level to improve inflammatory breast cancer diagnosis and management.Preventive medicine reports · 2023Article
- Article
- Differential Gene Expression of fresh tissue and patient-derived explants' matricellular proteins augment inflammatory breast cancer metastasis: the possible role of IL-6 and MCP-1.QJM : monthly journal of the Association of Physicians · 2023Article
- A Novel Preclinical Murine Model to Monitor Inflammatory Breast Cancer Tumor Growth and Lymphovascular Invasion.Cancers · 2023Article
- Stabilization of E-cadherin adhesions by COX-2/GSK3β signaling is a targetable pathway in metastatic breast cancer.JCI insight · 2023Article
- Metadherin Regulates Inflammatory Breast Cancer Invasion and Metastasis.International journal of molecular sciences · 2023Article
- Geometric tumor embolic budding characterizes inflammatory breast cancer.Breast cancer research and treatment · 2023Article
- PI3K/AKT/mTOR pathway and its related molecules participate in PROK1 silence-induced anti-tumor effects on pancreatic cancer.Open life sciences · 2023Article
- Adaptive stress response genes associated with breast cancer subtypes and survival outcomes reveal race-related differences.NPJ breast cancer · 2022Article
- Platelet Membrane: An Outstanding Factor in Cancer Metastasis.Membranes · 2022Review
- Comparative transcriptional analyses of preclinical models and patient samples reveal MYC and RELA driven expression patterns that define the molecular landscape of IBC.NPJ breast cancer · 2022Article
- Article
- A polycyclic aromatic hydrocarbon-enriched environmental chemical mixture enhances AhR, antiapoptotic signaling and a proliferative phenotype in breast cancer cells.Carcinogenesis · 2020Article
- In vitro vascularized tumor platform for modeling tumor-vasculature interactions of inflammatory breast cancer.Biotechnology and bioengineering · 2020Article
- PARP1 Inhibition Radiosensitizes Models of Inflammatory Breast Cancer to Ionizing Radiation.Molecular cancer therapeutics · 2019Article
- Pathological and molecular characteristics of inflammatory breast cancer.Translational cancer research · 2019Review
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9 authors at 4 institutions in 2 countries.
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Abstract
Inflammatory breast cancer (IBC) is one of the most lethal breast cancer variants; with existing therapy, 5-yr survival rate is only 35%. Current barriers to successful treatment of IBC include frequent infiltration and the presence of tumor cell clusters, termed tumor emboli, within the breast parenchyma and lymphatics. Prior studies have identified the role of anti-apoptotic signaling, in particular hyperactivation of NFκB and its target genes, in IBC pathobiology and therapeutic resistance. The objectives of this study were to: (1) determine if IBC tumor emboli express anti-apoptotic proteins and (2) develop a high content, multiparametric assay to assess the morphology of the IBC 3D spheroids and to optimize a high throughput format to screen for compounds that can inhibit the formation of the IBC tumor clusters/embolic structures. Immunohistochemical analysis of IBC patient tumor samples with documented tumor emboli revealed high NFκB (p65) staining along with expression of XIAP, a potent anti-apoptotic protein known to interact with NFκB signaling in enhancing survival of malignant cells. Subsequently, the high content assay developed allowed for simultaneous imaging and morphometric analysis, including count and viability of spheroids derived from SUM149, rSUM149 and SUM190 cells and its application to evaluate XIAP and NFκB inhibitory agents. We demonstrate the efficacy of the off-patent drug disulfiram when chelated with copper, which we had previously reported to inhibit NFκB signaling, was highly effective in disrupting both IBC spheroids and emboli grown in vitro. Taken together, these results identify a high-throughput approach to target tumor spheroid formation for drug discovery. Finally, disulfiram is a safe and approved drug for management of alcohol abuse, warranting its evaluation for repurposing in IBC therapy.
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