ArticleCell death discovery2023
Osimertinib induces paraptosis and TRIP13 confers resistance in glioblastoma cells.
Article in Cell death discovery, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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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
17 citing papers in PubMed, 21 citations in OpenAlex.
- Natural and Synthetic Compounds, Swords for Glioblastoma Therapy: From Tumor to Its Microenvironment.International journal of molecular sciences · 2026Review
- Photodynamic therapy mediates antitumor effects through multiple non‑apoptotic cell death pathways.Journal of biomedical science · 2026Review
- AAA ATPase TRIP13 is overexpressed in prostate cancer and promotes tumor progression.Translational oncology · 2026Article
- Crosstalk Between Autophagy and Paraptosis: A New Frontier in Cancer Therapy.International journal of molecular sciences · 2026Review
- Osimertinib activates TFEB to trigger hepatocyte cytoplasmic vacuolation-associated cell death.Cell communication and signaling : CCS · 2026Article
- A cyclometalated iridium(III) complex induces paraptotic cell death via mitochondrial dysfunction and ER stress in triple-negative breast cancer cells.Frontiers in pharmacology · 2026Article
- Discovery of novel antimyeloma agents targeting TRIP13 by molecular modeling and bioassay.RSC medicinal chemistry · 2025Article
- Evaluating the Antitumor Potential of Cannabichromene, Cannabigerol, and Related Compounds fromInternational journal of molecular sciences · 2025Article
- Application of EGFR-TKIs in brain tumors, a breakthrough in future?Journal of translational medicine · 2025Review
- Exploring paraptosis as a therapeutic approach in cancer treatment.Journal of biomedical science · 2024Review
- Natural products-induced cancer cell paraptosis.Food science & nutrition · 2024Article
- Paraptosis-A Distinct Pathway to Cell Death.International journal of molecular sciences · 2024Review
- TRIP13 Plays an Important Role in the Sensitivity of Leukemia Cell Response to Sulforaphane Therapy.ACS omega · 2024Article
- Targeting paraptosis in cancer: opportunities and challenges.Cancer gene therapy · 2024Review
- Small Molecule Tyrosine Kinase Inhibitors (TKIs) for Glioblastoma Treatment.International journal of molecular sciences · 2024Review
- Zearalenone Induces Blood-Testis Barrier Damage through Endoplasmic Reticulum Stress-Mediated Paraptosis of Sertoli Cells in Goats.International journal of molecular sciences · 2023Article
- Combined inhibition of lysine-specific demethylase 1 and kinase signaling as a preclinical treatment strategy in glioblastoma.Neuro-oncology advancesArticle
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
The efficacy of osimertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor, has been evaluated in glioblastoma (GBM) through preclinical and clinical trials. However, the underlying mechanism of osimertinib-induced GBM cell death and the underlying resistance mechanism to osimertinib remains unclear. Here, we demonstrate that Osimertinib induces paraptosis in GBM cells, as evidenced by the formation of cytoplasmic vacuoles, accumulation of ubiquitinated proteins, and upregulation of endoplasmic reticulum (ER) stress markers like CHOP. Additionally, neither apoptosis nor autophagy was involved in the osimertinib-induced cell death. RNAseq analysis revealed ER stress was the most significantly downregulated pathway upon exposure to osimertinib. Consistently, pharmacologically targeting the PERK-eIF2α axis impaired osimertinib-induced paraptosis. Notably, we show that the expression of thyroid receptor-interacting protein 13 (TRIP13), an AAA+ATPase, alleviated osimertinib-triggered paraptosis, thus conferring resistance. Intriguingly, MK-2206, an AKT inhibitor, downregulated TRIP13 levels and synergized with Osimertinib to suppress TRIP13-induced high GBM cell growth in vitro and in vivo. Together, our findings reveal a novel mechanism of action associated with the anti-GBM effects of osimertinib involving ER stress-regulated paraptosis. Furthermore, we identify a TRIP13-driven resistance mechanism against Osimertinib in GBM and offer a combination strategy using MK-2206 to overcome such resistance.
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.