ArticlePloS one2014
Relationships between signaling pathway usage and sensitivity to a pathway inhibitor: examination of trametinib responses in cultured breast cancer lines.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 27 citations in OpenAlex.
- Decoding breast cancer: insights into molecular pathways & therapeutic approaches.Discover oncology · 2025Review
- Signaling pathway dysregulation in breast cancer.Oncotarget · 2025Review
- sTPLS: identifying common and specific correlated patterns under multiple biological conditions.Briefings in bioinformatics · 2025Article
- Review
- Unveiling the impact of interferon genes on the immune microenvironment of triple-negative breast cancer: identification of therapeutic targets.Frontiers in bioinformatics · 2025Article
- Dual PI3K/mTOR inhibitor NVP-BEZ235 induces cell cycle arrest via autophagy mediated protein degradation of RPL19 in nephroblastoma cell.Frontiers in pharmacology · 2025Article
- Distinct mRNA expression profiles and miRNA regulators of the PI3K/AKT/mTOR pathway in breast cancer: insights into tumor progression and therapeutic targets.Frontiers in oncology · 2024Article
- Validating TDP1 as an Inhibition Target for the Development of Chemosensitizers for Camptothecin-Based Chemotherapy Drugs.Oncology and therapy · 2021Article
- Identification of a Triple Drug Combination That Is Synergistically Cytotoxic for Triple-Negative Breast Cancer Cells Using a Novel Combination Discovery Approach.SLAS discovery : advancing life sciences R & D · 2020Article
- Probing metabolic alterations in breast cancer in response to molecular inhibitors with Raman spectroscopy and validated with mass spectrometry.Chemical science · 2020Article
- Targeting Discoidin Domain Receptor 1 (DDR1) Signaling and Its Crosstalk with βInternational journal of molecular sciences · 2020Article
- Pyruvate anaplerosis is a mechanism of resistance to pharmacological glutaminase inhibition in triple-receptor negative breast cancer.BMC cancer · 2020Article
- Discovery and Characterisation of Dual Inhibitors of Tryptophan 2,3-Dioxygenase (TDO2) and Indoleamine 2,3-Dioxygenase 1 (IDO1) Using Virtual Screening.Molecules (Basel, Switzerland) · 2019Article
- Anti-tumor and anti-metastasis efficacy of E6201, a MEK1 inhibitor, in preclinical models of triple-negative breast cancer.Breast cancer research and treatment · 2019Article
- Investigation into Improving the Aqueous Solubility of the Thieno[2,3-b]pyridine Anti-Proliferative Agents.Molecules (Basel, Switzerland) · 2018Article
- Derivation of Breast Cancer Cell Lines Under Physiological (5%) Oxygen Concentrations.Frontiers in oncology · 2018Article
- Endocrine Therapy of Estrogen Receptor-Positive Breast Cancer Cells: Early Differential Effects on Stem Cell Markers.Frontiers in oncology · 2017Article
- Evidence that phospholipase C is involved in the antitumour action of NSC768313, a new thieno[2,3-b]pyridine derivative.Cancer cell international · 2016Article
- Differences in MEK inhibitor efficacy in molecularly characterized low-grade serous ovarian cancer cell lines.American journal of cancer research · 2016Article
- Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cellular signaling pathways involving mTOR, PI3K and ERK have dominated recent studies of breast cancer biology, and inhibitors of these pathways have formed a focus of numerous clinical trials. We have chosen trametinib, a drug targeting MEK in the ERK pathway, to address two questions. Firstly, does inhibition of a signaling pathway, as measured by protein phosphorylation, predict the antiproliferative activity of trametinib? Secondly, do inhibitors of the mTOR and PI3K pathways synergize with trametinib in their effects on cell proliferation? A panel of 30 human breast cancer cell lines was chosen to include lines that could be classified according to whether they were ER and PR positive, HER2 over-expressing, and "triple negative". Everolimus (targeting mTOR), NVP-BEZ235 and GSK2126458 (both targeting PI3K/mTOR) were chosen for combination experiments. Inhibition of cell proliferation was measured by IC50 values and pathway utilization was measured by phosphorylation of signaling kinases. Overall, no correlation was found between trametinib IC50 values and inhibition of ERK signaling. Inhibition of ERK phosphorylation was observed at trametinib concentrations not affecting proliferation, and sensitivity of cell proliferation to trametinib was found in cell lines with low ERK phosphorylation. Evidence was found for synergy between trametinib and either everolimus, NVP-BEZ235 or GSK2126458, but this was cell line specific. The results have implications for the clinical application of PI3K/mTOR and MEK inhibitors.
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