ArticleOncotarget2015
Endoplasmic reticulum targeting in Ewing's sarcoma by the alkylphospholipid analog edelfosine.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 24 citations in OpenAlex.
- Unfolded Protein Response as a Therapeutic Target: 4-(Heptyloxy)phenol Induces Programmed Cell Death in Ewing Sarcoma.Molecular cancer therapeutics · 2026Article
- Edelfosine induces cell cycle arrest and apoptosis in vascular smooth muscle cells to suppress neointimal hyperplasia.Scientific reports · 2026Article
- SIR telomere silencing depends on nuclear envelope lipids and modulates sensitivity to a lysolipid.The Journal of cell biology · 2023Article
- Clusters of apoptotic signaling molecule-enriched rafts, CASMERs: membrane platforms for protein assembly in Fas/CD95 signaling and targets in cancer therapy.Biochemical Society transactions · 2022Article
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- Review
- Neutrophils drive endoplasmic reticulum stress-mediated apoptosis in cancer cells through arginase-1 release.Scientific reports · 2021Article
- Mitochondrial Targeting Involving Cholesterol-Rich Lipid Rafts in the Mechanism of Action of the Antitumor Ether Lipid and Alkylphospholipid Analog Edelfosine.Pharmaceutics · 2021Review
- Drug delivery nanocarriers and recent advances ventured to improve therapeutic efficacy against osteosarcoma: an overview.Journal of the Egyptian National Cancer Institute · 2021Review
- Lipid rafts as signaling hubs in cancer cell survival/death and invasion: implications in tumor progression and therapy: Thematic Review Series: Biology of Lipid Rafts.Journal of lipid research · 2020Review
- Doxorubicin and Edelfosine Combo-Loaded Lipid-Polymer Hybrid Nanoparticles for Synergistic Anticancer Effect Against Drug-Resistant Osteosarcoma.OncoTargets and therapy · 2020Article
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Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ewing's sarcoma (ES) is the second most common bone cancer in children and young people. Edelfosine (1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine) is the prototype of a family of synthetic antitumor compounds, collectively known as alkylphospholipid analogs (APLs). We have found that APLs ranked edelfosine>perifosine>erucylphosphocholine>miltefosine for their capacity to promote apoptosis in ES cells. Edelfosine accumulated in the endoplasmic reticulum (ER) and triggered an ER stress response that eventually led to caspase-dependent apoptosis in ES cells. This apoptotic response involved mitochondrial-mediated processes, with cytochrome c release, caspase-9 activation and generation of reactive oxygen species. Edelfosine-induced apoptosis was also dependent on sustained c-Jun NH2-terminal kinase activation. Oral administration of edelfosine showed a potent in vivo antitumor activity in an ES xenograft animal model. Histochemical staining gave evidence for ER stress response and apoptosis in the ES tumors isolated from edelfosine-treated mice. Edelfosine showed a preferential action on ES tumor cells as compared to non-transformed osteoblasts, and appeared to be well suited for combination therapy regimens. These results demonstrate in vitro and in vivo antitumor activity of edelfosine against ES cells that is mediated by caspase activation and ER stress, and provide the proof of concept for a putative edelfosine- and ER stress-mediated approach forES treatment.
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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.