ArticlePloS one2014
mTOR inhibition induces compensatory, therapeutically targetable MEK activation in renal cell carcinoma.
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 18 papers.
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Who cites it
18 citing papers in PubMed, 26 citations in OpenAlex.
- RHEBL1 expression is activated by the Oct4-Sox2 complex in oral squamous cell carcinoma.Functional & integrative genomics · 2026Article
- Synthesis and Biological Evaluation of MEK/mTOR Multifunctional Inhibitors as Novel Anticancer Agents.Journal of medicinal chemistry · 2025Article
- Intravesical instillation-based mTOR-STAT3 dual targeting for bladder cancer treatment.Journal of experimental & clinical cancer research : CR · 2024Article
- Rapamycin limits CD4+ T cell proliferation in simian immunodeficiency virus-infected rhesus macaques on antiretroviral therapy.The Journal of clinical investigation · 2022Article
- Activation of ERK and p38 Reduces AZD8055-Mediated Inhibition of Protein Synthesis in Hepatocellular Carcinoma HepG2 Cell Line.International journal of molecular sciences · 2021Article
- Functional and genomic characterization of patient-derived xenograft model to study the adaptation to mTORC1 inhibitor in clear cell renal cell carcinoma.Cancer medicine · 2021Article
- Genomic and pathological heterogeneity in clinically diagnosed small cell lung cancer in never/light smokers identifies therapeutically targetable alterations.Molecular oncology · 2021Article
- Is Structure-Based Drug Design Ready for Selectivity Optimization?Journal of chemical information and modeling · 2020Article
- MEK inhibition overcomes everolimus resistance in gastric cancer.Cancer chemotherapy and pharmacology · 2020Article
- Possible Novel Therapeutic Targets in Lymphangioleiomyomatosis Treatment.Frontiers in medicine · 2020Review
- Naturally Occurring Canine Melanoma as a Predictive Comparative Oncology Model for Human Mucosal and Other Triple Wild-Type Melanomas.International journal of molecular sciences · 2018Review
- RAPTOR up-regulation contributes to resistance of renal cancer cells to PI3K-mTOR inhibition.PloS one · 2018Article
- Prognostic value of copper transporter 1 expression in patients with clear cell renal cell carcinoma.Oncology letters · 2017Article
- The selective MEK1 inhibitor Selumetinib enhances the antitumor activity of everolimus against renal cell carcinoma in vitro and in vivo.Oncotarget · 2017Article
- Synergistic targeted inhibition of MEK and dual PI3K/mTOR diminishes viability and inhibits tumor growth of canine melanoma underscoring its utility as a preclinical model for human mucosal melanoma.Pigment cell & melanoma research · 2016Article
- The epidermal growth factor receptor pathway in chronic kidney diseases.Nature reviews. Nephrology · 2016Review
- MiR-144 inhibits cell proliferation of renal cell carcinoma by targeting MTOR.Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban · 2016Article
- Synergistic roles of p53 and HIF1α in human renal cell carcinoma-cell apoptosis responding to the inhibition of mTOR and MDM2 signaling pathways.Drug design, development and therapy · 2016Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Rapamycin derivatives allosterically targeting mTOR are currently FDA approved to treat advanced renal cell carcinoma (RCC), and catalytic inhibitors of mTOR/PI3K are now in clinical trials for treating various solid tumors. We sought to investigate the relative efficacy of allosteric versus catalytic mTOR inhibition, evaluate the crosstalk between the mTOR and MEK/ERK pathways, as well as the therapeutic potential of dual mTOR and MEK inhibition in RCC. Pharmacologic (rapamycin and BEZ235) and genetic manipulation of the mTOR pathway were evaluated by in vitro assays as monotherapy as well as in combination with MEK inhibition (GSK1120212). Catalytic mTOR inhibition with BEZ235 decreased proliferation and increased apoptosis better than allosteric mTOR inhibition with rapamycin. While mTOR inhibition upregulated MEK/ERK signaling, concurrent inhibition of both pathways had enhanced therapeutic efficacy. Finally, primary RCC tumors could be classified into subgroups [(I) MEK activated, (II) Dual MEK and mTOR activated, (III) Not activated, and (IV) mTOR activated] based on their relative activation of the PI3K/mTOR and MEK pathways. Patients with mTOR only activated tumors had the worst prognosis. In summary, dual targeting of the mTOR and MEK pathways in RCC can enhance therapeutic efficacy and primary RCC can be subclassified based on their relative levels of mTOR and MEK activation with potential therapeutic implications.
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