ArticlePloS one2015
Potentiation of Growth Inhibitory Responses of the mTOR Inhibitor Everolimus by Dual mTORC1/2 Inhibitors in Cultured Breast Cancer Cell Lines.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
29 citing papers in PubMed.
- Breast cancer-associated fibroblast-derived exosomal miR-1290 promotes triple-negative breast cancer cell proliferation.Signal transduction and targeted therapy · 2026Article
- Real-time cell viability monitoring for high-throughput drug screening using tumor xenograft-derived cells.Cell reports methods · 2026Article
- Molecularly Targeted Therapies in Oncology: Mechanisms, Resistance, and Combination Strategies.Molecules (Basel, Switzerland) · 2026Review
- Molecular pathways in reproductive cancers: a focus on prostate and ovarian cancer.Cancer cell international · 2025Review
- Progress in Glioma Stem Cell Research.Cancers · 2023Review
- Expression Modulation of Immune Checkpoint Molecules by Ibrutinib and Everolimus Through STAT3 in MCF-7 Breast Cancer Cells.Iranian journal of pharmaceutical research : IJPR · 2022Article
- Rapamycin synergizes the cytotoxic effects of MEK inhibitor binimetinib and overcomes acquired resistance to therapy in melanoma cell lines in vitro.Investigational new drugs · 2021Article
- Role of intracellular signaling pathways and their inhibitors in the treatment of inflammation.Inflammopharmacology · 2021Review
- Landscapes of cellular phenotypic diversity in breast cancer xenografts and their impact on drug response.Nature communications · 2021Article
- MTOR promotes basal cell carcinoma growth through atypical PKC.Experimental dermatology · 2021Article
- The anti-tubercular activity of simvastatin is mediated by cholesterol-driven autophagy via the AMPK-mTORC1-TFEB axis.Journal of lipid research · 2020Article
- Exploring treatment with Ribociclib alone or in sequence/combination with Everolimus in ERBMC cancer · 2020Article
- Upregulation of Peroxiredoxin-2 in Well-Differentiated Pancreatic Neuroendocrine Tumors and Its Utility as a Biomarker for Predicting the Response to Everolimus.Antioxidants (Basel, Switzerland) · 2020Article
- Signal Transduction Pathways in Breast Cancer: The Important Role of PI3K/Akt/mTOR.Journal of oncology · 2020Review
- 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
- An In silico Approach to Identify High Affinity Small Molecule Targeting m-TOR Inhibitors for the Clinical Treatment of Breast CancerAsian Pacific journal of cancer prevention : APJCP · 2019Article
- MNK1 inhibitor CGP57380 overcomes mTOR inhibitor-induced activation of eIF4E: the mechanism of synergic killing of human T-ALL cells.Acta pharmacologica Sinica · 2018Article
- A Limited Sampling Strategy to Estimate Exposure of Everolimus in Whole Blood and Peripheral Blood Mononuclear Cells in Renal Transplant Recipients Using Population Pharmacokinetic Modeling and Bayesian Estimators.Clinical pharmacokinetics · 2018Article
- Everolimus inhibits breast cancer cell growth through PI3K/AKT/mTOR signaling pathway.Molecular medicine reports · 2018Article
- Derivation of Breast Cancer Cell Lines Under Physiological (5%) Oxygen Concentrations.Frontiers in oncology · 2018Article
Corrections and comments
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The mammalian target of rapamycin (mTOR), a vital component of signaling pathways involving PI3K/AKT, is an attractive therapeutic target in breast cancer. Everolimus, an allosteric mTOR inhibitor that inhibits the mTOR functional complex mTORC1, is approved for treatment of estrogen receptor positive (ER+) breast cancer. Other mTOR inhibitors show interesting differences in target specificities: BEZ235 and GSK2126458 are ATP competitive mTOR inhibitors targeting both PI3K and mTORC1/2; AZD8055, AZD2014 and KU-0063794 are ATP competitive mTOR inhibitors targeting both mTORC1 and mTORC2; and GDC-0941 is a pan-PI3K inhibitor. We have addressed the question of whether mTOR inhibitors may be more effective in combination than singly in inhibiting the proliferation of breast cancer cells. We selected a panel of 30 human breast cancer cell lines that included ER and PR positive, HER2 over-expressing, and "triple negative" variants, and determined whether signaling pathway utilization was related to drug-induced inhibition of proliferation. A significant correlation (p = 0.005) was found between everolimus IC50 values and p70S6K phosphorylation, but not with AKT or ERK phosphorylation, consistent with the mTOR pathway being a principal target. We then carried out combination studies with four everolimus resistant triple-negative breast cancer cell lines, and found an unexpectedly high degree of synergy between everolimus and the other inhibitors tested. The level of potentiation of everolimus inhibitory activity (measured by IC50 values) was found to be cell line-specific for all the kinase inhibitors tested. The results suggest that judicious combination of mTOR inhibitors with different modes of action could have beneficial effects in the treatment of breast cancer.
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