ArticleCancer discovery2011
Oncogenic EGFR signaling activates an mTORC2-NF-κB pathway that promotes chemotherapy resistance.
Article in Cancer discovery, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 187 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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
187 citing papers in PubMed, 278 citations in OpenAlex.
- Phase II trial of dacomitinib, a pan-human EGFR tyrosine kinase inhibitor, in recurrent glioblastoma patients with EGFR amplification.Neuro-oncology · 2017Trial
- PML mediates glioblastoma resistance to mammalian target of rapamycin (mTOR)-targeted therapies.Proceedings of the National Academy of Sciences of the United States of America · 2013Trial
- CPT1A-mediated IDO1 succinylation shapes EGFRvIII-driven resistance to tumor electric field therapy in glioblastoma.Nature communications · 2026Article
- Epigenetically elevated RAD51AP1 regulates the RAD51-UAF1 complex contributing to temozolomide resistance in EGFRvIII glioblastoma.Chinese medical journal · 2026Article
- Overcoming blood-brain barrier and chemoresistance in glioblastoma by Angiopep-2-modified NK cell-derived extracellular vesicles for targeted delivery of temozolomide.Journal of nanobiotechnology · 2026Article
- CMTM6/PD-L1-targeted AAV promotes anti-tumor immune responses and chemotherapy responsiveness.Frontiers in immunology · 2026Article
- Emerging frontiers in glioma therapy: the evolving role of glioma vaccines.Frontiers in immunology · 2026Review
- Rictor orchestrates β-catenin/FOXO balance by maintaining redox homeostasis during development of ovarian cancer.Oncogene · 2025Article
- Dual nuclear receptor 4A1 (NR4A1/NR4A2) ligands inhibit glioblastoma growth and target TWIST1.Molecular pharmacology · 2025Article
- ArfGAP with the SH3 Domain, Ankyrin Repeat and PH Domain 1 Inversely Regulates Programmed Death-Ligand 1 Through Negative Feedback of Phosphorylated Epithelial Growth Factor Receptor and Activation of Nuclear Factor-Kappa B in Non-Small Cell Lung Cancer.Cancer management and research · 2025Article
- Unveiling the Role of Mechanistic Target of Rapamycin Kinase (MTOR) Signaling in Cancer Progression and the Emergence of MTOR Inhibitors as Therapeutic Strategies.ACS pharmacology & translational science · 2024Review
- Deciphering the topological landscape of glioma using a network theory framework.Scientific reports · 2024Article
- Plasma Cell-Free DNA Concentration and Fragmentomes Predict Neoadjuvant Chemotherapy Response in Cervical Cancer Patients.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Cellular senescence in metastatic prostate cancer: A therapeutic opportunity or challenge (Review).Molecular medicine reports · 2024Review
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- Immunosurveillance encounters cancer metabolism.EMBO reports · 2024Review
- Progress in Glioma Stem Cell Research.Cancers · 2023Review
- Article
- STAT3/LKB1 controls metastatic prostate cancer by regulating mTORC1/CREB pathway.Molecular cancer · 2023Article
127 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
23 authors at 8 institutions in 1 country.
Funding
Abstract
unlabelledAlthough it is known that mTOR complex 2 (mTORC2) functions upstream of Akt, the role of this protein kinase complex in cancer is not well understood. Through an integrated analysis of cell lines, in vivo models, and clinical samples, we demonstrate that mTORC2 is frequently activated in glioblastoma (GBM), the most common malignant primary brain tumor of adults. We show that the common activating epidermal growth factor receptor (EGFR) mutation (EGFRvIII) stimulates mTORC2 kinase activity, which is partially suppressed by PTEN. mTORC2 signaling promotes GBM growth and survival and activates NF-κB. Importantly, this mTORC2-NF-κB pathway renders GBM cells and tumors resistant to chemotherapy in a manner independent of Akt. These results highlight the critical role of mTORC2 in the pathogenesis of GBM, including through the activation of NF-κB downstream of mutant EGFR, leading to a previously unrecognized function in cancer chemotherapy resistance. These findings suggest that therapeutic strategies targeting mTORC2, alone or in combination with chemotherapy, will be effective in the treatment of cancer. SIGNIFICANCE: This study demonstrates that EGFRvIII-activated mTORC2 signaling promotes GBM proliferation, survival, and chemotherapy resistance through Akt-independent activation of NF-κB. These results highlight the role of mTORC2 as an integrator of two canonical signaling networks that are commonly altered in cancer, EGFR/phosphoinositide-3 kinase (PI3K) and NF-κB. These results also validate the importance of mTORC2 as a cancer target and provide new insights into its role in mediating chemotherapy resistance, suggesting new treatment strategies.
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Registered trials
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.