ArticleDrug design, development and therapy2018
Attenuation of everolimus-induced cytotoxicity by a protective autophagic pathway involving ERK activation in renal cell carcinoma cells.
Article in Drug design, development and therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
13 citing papers in PubMed, 19 citations in OpenAlex.
- An overview of autophagy inhibition as a potential clinical strategy in cancer therapy.Molecular pharmacology · 2025Review
- Review
- Methuosis Inducer SGI-1027 Cooperates with Everolimus to Promote Apoptosis and Pyroptosis by Triggering Lysosomal Membrane Permeability in Renal Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Depletion of CPNE7 sensitizes colorectal cancer to 5-fluorouracil by downregulating ATG9B expression.Journal of cellular and molecular medicine · 2024Article
- Three generations of mTOR kinase inhibitors in the activation of the apoptosis process in melanoma cells.Journal of cell communication and signaling · 2023Article
- Integrated bioinformatic analysis and cell line experiments reveal the significant role of the novel immune checkpoint TIGIT in kidney renal clear cell carcinoma.Frontiers in oncology · 2023Article
- IFI35 Promotes Renal Cancer Progression by Inhibiting pSTAT1/pSTAT6-Dependent Autophagy.Cancers · 2022Article
- Repurposing ketoconazole as an exosome directed adjunct to sunitinib in treating renal cell carcinoma.Scientific reports · 2021Article
- The KRASCancer discovery · 2020Article
- Review
- Everolimus inhibits the proliferation and migration of epidermal growth factor receptor-resistant lung cancer cells A549 via regulating the microRNA-4328/phosphatase and tensin homolog signaling pathway.Oncology letters · 2019Article
- mTOR inhibitor Everolimus-induced apoptosis in melanoma cells.Journal of cell communication and signaling · 2019Article
- Inhibiting Autophagy in Renal Cell Cancer and the Associated Tumor Endothelium.Cancer journal (Sudbury, Mass.)Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimThe mammalian target of rapamycin (mTOR) pathway is a critical target for cancer treatment and the mTOR inhibitor everolimus (RAD001) has been approved for treatment of renal cell carcinoma (RCC). However, the limited efficacy of RAD001 has led to the development of drug resistance. Autophagy is closely related to cell survival and death, which may be activated under RAD001 stimulation. The aim of the present study was to identify the underlying mechanisms of RAD001 resistance in RCC cells through cytoprotective autophagy involving activation of the extracellular signal-regulated kinase (ERK) pathway. METHODS AND
resultsRAD001 strongly induced autophagy of RCC cells in a dose- and time-dependent manner, as confirmed by Western blot analysis. Importantly, suppression of autophagy by the pharmacological inhibitor chloroquine effectively enhanced RAD001-induced apoptotic cytotoxicity, as demonstrated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and Western blot analysis, indicating a cytoprotective role for RAD001-induced autophagy. In addition, as was shown by the MTT assay, flow cytometry, and Western blot analysis, RAD001 robustly activated ERK, but not c-Jun N-terminal kinase and p38. Activation of ERK was inhibited by the pharmacological inhibitor selumetinib (AZD6244), which effectively promoted RAD001-induced cell death. Moreover, employing AZD6244 markedly attenuated RAD001-induced autophagy and enhanced RAD001-induced apoptosis, which play a central role in RAD001-induced cell death. Furthermore, RAD001-induced autophagy is regulated by ERK-mediated phosphorylation of Beclin-1 and B-cell lymphoma 2, as confirmed by Western blot analysis.
conclusionThese results suggest that RAD001-induced autophagy involves activation of the ERK, which may impair cytotoxicity of RAD001 in RCC cells. Thus, inhibition of the activation of ERK pathway-mediated autophagy may be useful to overcome chemoresistance to RAD001.
Indexed as
Identifiers
What OpenQuestion holds
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.