ArticleBreast cancer research and treatment2019
Anti-tumor and anti-metastasis efficacy of E6201, a MEK1 inhibitor, in preclinical models of triple-negative breast cancer.
Article in Breast cancer research and treatment, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 13 papers.
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13 citing papers in PubMed, 25 citations in OpenAlex.
- Comprehensive pan-cancer analysis of USP35 and validation of its role in gastric cancer.Human genomics · 2025Article
- Small Molecule Therapeutics in the Pipeline Targeting for Triple-Negative Breast Cancer: Origin, Challenges, Opportunities, and Mechanisms of Action.International journal of molecular sciences · 2024Review
- CircZCCHC2 decreases pirarubicin sensitivity and promotes triple-negative breast cancer development via the miR-1200/TPR axis.iScience · 2024Article
- Three generations of mTOR kinase inhibitors in the activation of the apoptosis process in melanoma cells.Journal of cell communication and signaling · 2023Article
- Development of a cancer metastasis-on-chip assay for high throughput drug screening.Frontiers in oncology · 2023Article
- Target Identification of 22-(4-Pyridinecarbonyl) Jorunnamycin A, a Tetrahydroisoquinoline Derivative from the SpongeMolecules (Basel, Switzerland) · 2022Article
- B7 homolog 3 induces lung metastasis of breast cancer through Raf/MEK/ERK axis.Breast cancer research and treatment · 2022Article
- Inhibitors of PD-1/PD-L1 and ERK1/2 impede the proliferation of receptor positive and triple-negative breast cancer cell lines.Journal of cancer research and clinical oncology · 2021Article
- Imbalance of Molecular Module of TINCR-miR-761 Promotes the Metastatic Potential of Early Triple Negative Breast Cancer and Partially Offsets the Anti-Tumor Activity of Luteolin.Cancer management and research · 2021Article
- Proteomic analysis of circulating extracellular vesicles identifies potential markers of breast cancer progression, recurrence, and response.Science advances · 2020Article
- Molecular subtypes and precision treatment of triple-negative breast cancer.Annals of translational medicine · 2020Review
- The Fluoro-Thiazolylhydrazone Compound TSC-3C Inhibits Triple Negative Breast Cancer (TNBC) Cell Line Activity by Promoting Apoptosis, Regulating the MAPK Pathway and Inducing Mitochondrial Dysfunction.International journal of molecular sciences · 2020Article
- Protein phosphatase 2A activation as a therapeutic strategy for managing MYC-driven cancers.The Journal of biological chemistry · 2020Article
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
purposeTriple-negative breast cancer (TNBC) lacks the receptor targets estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2, and thus, it does not respond to receptor-targeted treatments. TNBC has higher recurrence, metastasis, and mortality rates than other subtypes of breast cancer. Mounting data suggest that the MAPK (also known as RAS-RAF-MEK-ERK) pathway is an important therapeutic target in TNBC.
methodsTo evaluate anti-tumor and anti-metastasis efficacy of E6201, we used cell proliferation assay, soft agar assay, cell cycle assay, Annexin V staining assay, immunoblotting analysis, immunohistochemistry, migration assay, invasion assay, mammary fat pad xenograft, and experimental and spontaneous metastasis xenograft models. We also evaluated the anti-tumor efficacy of E6201 plus CDK4/6 inhibitor, mTOR inhibitor, or ATR inhibitor.
resultsE6201 inhibited TNBC cell colony formation, migration, and invasion in a dose-dependent manner. E6201 induced G1 cell cycle arrest and apoptosis. E6201 inhibited TNBC xenograft growth and inhibited TNBC lung metastasis and improved mouse survival in experimental metastasis and spontaneous metastasis assays. Immunohistochemical staining demonstrated that E6201 decreased the metastatic burden in the lung and decreased phosphorylated ERK expression in a dose-dependent manner. Combination of E6201 with CDK4/6 inhibitor or mTOR inhibitor enhanced E6201's in vitro anti-tumor efficacy.
conclusionThese results indicate that E6201 exhibits anti-tumor efficacy against TNBC in vitro and anti-metastasis efficacy against TNBC in vivo. These results provide a rationale for further clinical development of E6201 as a MAPK-pathway-targeted therapy for TNBC.
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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.