ArticleOncotarget2016
CGP57380 enhances efficacy of RAD001 in non-small cell lung cancer through abrogating mTOR inhibition-induced phosphorylation of eIF4E and activating mitochondrial apoptotic pathway.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 57 citations in OpenAlex.
- MicroRNA-150-3p enhances the antitumour effects of CGP57380 and is associated with a favourable prognosis in non-small cell lung cancer.Scientific reports · 2025Article
- MNK: A Novel Promising Target for Cancer Immunotherapy.Current medicinal chemistry · 2025Review
- CEACAM1 increased the lymphangiogenesis through miR-423-5p and NF- kB in Non-Small Cell Lung Cancer.Biochemistry and biophysics reports · 2024Article
- The role of eIF4F-driven mRNA translation in regulating the tumour microenvironment.Nature reviews. Cancer · 2023Review
- An Aptamer against MNK1 for Non-Small Cell Lung Cancer Treatment.Pharmaceutics · 2023Article
- Overexpressed p-S6 associates with lymph node metastasis and predicts poor prognosis in non-small cell lung cancer.BMC cancer · 2022Article
- Exosome-mediated miR-7-5p delivery enhances the anticancer effect of Everolimus via blocking MNK/eIF4E axis in non-small cell lung cancer.Cell death & disease · 2022Article
- XPO1-Mediated EIF1AX Cytoplasmic Relocation Promotes Tumor Migration and Invasion in Endometrial Carcinoma.Oxidative medicine and cellular longevity · 2022Article
- Overexpression of p-4EBP1 associates with p-eIF4E and predicts poor prognosis for non-small cell lung cancer patients with resection.PloS one · 2022Article
- The plasticity of mRNA translation during cancer progression and therapy resistance.Nature reviews. Cancer · 2021Review
- MNK Inhibition SensitizesCancer discovery · 2021Article
- Overexpression of HSP10 correlates with HSP60 and Mcl-1 levels and predicts poor prognosis in non-small cell lung cancer patients.Cancer biomarkers : section A of Disease markers · 2021Article
- Overexpression of FADD and Bcl-XS proteins as novel prognostic biomarkers for surgically resected non-small cell lung cancer.Cancer biomarkers : section A of Disease markers · 2021Article
- NCAPH is negatively associated with Mcl‑1 in non‑small cell lung cancer.Molecular medicine reports · 2020Article
- Phosphorylation of the mRNA cap-binding protein eIF4E and cancer.Cellular signalling · 2020Review
- miR-4634 augments the anti-tumor effects of RAD001 and associates well with clinical prognosis of non-small cell lung cancer.Scientific reports · 2020Article
- Review
- The deubiquitinase USP22 regulates PD-L1 degradation in human cancer cells.Cell communication and signaling : CCS · 2020Article
- Deeping in the Role of the MAP-Kinases Interacting Kinases (MNKs) in Cancer.International journal of molecular sciences · 2020Review
- mTOR Signaling at the Crossroad between Metazoan Regeneration and Human Diseases.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The mammalian target of rapamycin (mTOR) is a potentially important therapeutic target in a broad range of cancer types. mTOR inhibitors such as rapamycin and its analogs (rapalogs) have been proven effective as anticancer agents in non-small cell lung cancer (NSCLC), whereas they strongly enhance phosphorylation of eukaryotic translation initiation factor 4E (eIF4E) and activation of Akt, which cause resistance to mTOR-targeted therapy after an initial response. Rapamycin induces eIF4E phosphorylation by activating MAPK-interacting kinases (Mnks), and therefore targeting Mnk/eIF4E pathway represents a potential therapeutic strategy for the treatment of NSCLC. Here, our results showed that over-expression of p-Mnk1 and p-eIF4E was significantly associated with poor overall survival of NSCLC patients and high expression of p-Mnk1 might act as an independent prognostic biomarker for these patients. Meanwhile, inhibiting Mnk1 expression by Mnk inhibitor (CGP57380) could abrogate rapalogs (RAD001)-induced eIF4E phosphorylation and Akt activation. Furthermore, combination of CGP57380 and RAD001 could induce NSCLC cells apoptosis via activating intrinsic mitochondrial pathway, and exert synergistic antitumor efficacy both in vitro and in vivo. In conclusion, combination of targeting both mTOR and Mnk/eIF4E signaling pathways to enhance effectiveness of mTOR-targeted cancer therapy might be significant innovation for the personalized treatment of NSCLC.
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