ArticleMolecular cancer therapeutics2015
MEK Inhibitor Selumetinib (AZD6244; ARRY-142886) Prevents Lung Metastasis in a Triple-Negative Breast Cancer Xenograft Model.
Article in Molecular cancer therapeutics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.
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Who cites it
48 citing papers in PubMed, 1 synthesis or guideline pooled it, 68 citations in OpenAlex.
- Drug repurposing based on differentially expressed genes suggests drug combinations with possible synergistic effects in treatment of lung adenocarcinoma.Cancer biology & therapy · 2023Pooled it
- Cryptotanshinone Directly Targets MEK1 to Inhibit Migration and Invasion of Breast Cancer Cells Through Down-Regulating ERK/EMT Axis.Phytotherapy research : PTR · 2026Article
- Inhibition of MCL-1 and MEK Overcomes MEK Inhibitor Resistance in Triple-Negative and Inflammatory Breast Cancers.Molecular cancer therapeutics · 2025Article
- Bridging molecular insights and clinical application: non-coding RNAs, targeted drug delivery, and metastatic breast cancer therapy.Discover oncology · 2025Review
- Glioma-Derived Exosomes and Their Application as Drug Nanoparticles.International journal of molecular sciences · 2024Review
- Single-cell transcriptional atlas of human breast cancers and model systems.Clinical and translational medicine · 2024Article
- Beyond Anti-PD-1/PD-L1: Improving Immune Checkpoint Inhibitor Responses in Triple-Negative Breast Cancer.Cancers · 2024Review
- A review of biological targets and therapeutic approaches in the management of triple-negative breast cancer.Journal of advanced research · 2023Review
- MicroRNA-Based Discovery of Biomarkers, Therapeutic Targets, and Repositioning Drugs for Breast Cancer.Cells · 2023Article
- Molecular signaling network and therapeutic developments in breast cancer brain metastasis.Advances in cancer biology - metastasis · 2023Article
- Targeting Nitric Oxide: Say NO to Metastasis.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Review
- Upregulation of the EGFR/MEK1/MAPK1/2 signaling axis as a mechanism of resistance to antiestrogen‑induced BimEL dependent apoptosis in ERInternational journal of oncology · 2023Article
- Article
- Glioblastoma-Derived Exosomes as Nanopharmaceutics for Improved Glioma Treatment.Pharmaceutics · 2022Article
- Therapeutic progress and challenges for triple negative breast cancer: targeted therapy and immunotherapy.Molecular biomedicine · 2022Review
- Perspectives on the role of breast cancer susceptibility gene in breast cancer.International journal of clinical oncology · 2022Article
- Article
- Novel RAF/MEK inhibitor CH5126766/VS-6766 has efficacy in combination with eribulin for the treatment of triple-negative breast cancer.Cancer science · 2021Article
- Deciphering molecular mechanisms of metastasis: novel insights into targets and therapeutics.Cellular oncology (Dordrecht, Netherlands) · 2021Review
- Precision Medicine and Triple-Negative Breast Cancer: Current Landscape and Future Directions.Cancers · 2021Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Patients with triple-negative breast cancer (TNBC) have a poor prognosis because TNBC often metastasizes, leading to death. Among patients with TNBC, those with extracellular signal-regulated kinase 2 (ERK2)-overexpressing tumors were at higher risk of death than those with low-ERK2-expressing tumors (hazard ratio, 2.76; 95% confidence interval, 1.19-6.41). The MAPK pathway has been shown to be a marker of breast cancer metastasis, but has not been explored as a potential therapeutic target for preventing TNBC metastasis. Interestingly, when we treated TNBC cells with the allosteric MEK inhibitor selumetinib, cell viability was not reduced in two-dimensional culture. However, in three-dimensional culture, selumetinib changed the mesenchymal phenotype of TNBC cells to an epithelial phenotype. Cells that undergo epithelial-mesenchymal transition (EMT) are thought to contribute to the metastatic process. EMT leads to generation of mesenchymal-like breast cancer cells with stem cell-like characteristics and a CD44(+)CD24(-/low) expression pattern. We tested the hypothesis that targeted inhibition of the MAPK pathway by selumetinib inhibits acquisition of the breast cancer stem cell phenotype and prevents lung metastasis of TNBC. TNBC cells treated with selumetinib showed inhibition of anchorage-independent growth, an indicator of in vivo tumorigenicity (P < 0.005), and decreases in the CD44(+)CD24(-/low) fraction, ALDH1 activity, and mammosphere-forming efficiency. Mice treated with selumetinib formed significantly fewer lung metastases than control mice injected with vehicle (P < 0.05). Our data demonstrate that MEK inhibitors can inhibit breast cancer stem cells and may have clinical potential for the prevention of metastasis in certain cases in which tumors are MAPK dependent.
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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.