ArticleTranslational oncology2019
The Third-Generation EGFR Inhibitor, Osimertinib, Promotes c-FLIP Degradation, Enhancing Apoptosis Including TRAIL-Induced Apoptosis in NSCLC Cells with Activating EGFR Mutations.
Article in Translational oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- Adjuvant EGFR-TKIs for Patients With Resected EGFR-Mutant Non-Small Cell Lung Cancer: A Meta-Analysis of 1,283 Patients.Frontiers in oncology · 2021Pooled it
- Cancer-associated fibroblasts promote osimertinib resistance in non-small cell lung cancer cells via METTL1-mediated NET1 mCell death & disease · 2026Article
- Tetrahydrocurcumin targets TRIP13 inhibiting the interaction of TRIP13/USP7/c-FLIP to mediate c-FLIP ubiquitination in triple-negative breast cancer.Journal of advanced research · 2025Article
- Cell Death, Molecular Targeted Therapies, and Metabolic Reprogramming in EGFR-Mutant Lung Cancer.Cancers · 2025Review
- EGFR mutations in non-small cell lung cancer: Classification, characteristics and resistance to third-generation EGFR-tyrosine kinase inhibitors (Review).Oncology letters · 2025Review
- Article
- Beyond Death: Unmasking the Intricacies of Apoptosis Escape.Molecular diagnosis & therapy · 2024Review
- High-dose short-term osimertinib treatment is effective in patient-derived metastatic colorectal cancer organoids.BJC reports · 2024Article
- The impact of adjuvant EGFR-TKIs and 14-gene molecular assay on stage I non-small cell lung cancer with sensitive EGFR mutations.EClinicalMedicine · 2023Article
- Osimertinib induces paraptosis and TRIP13 confers resistance in glioblastoma cells.Cell death discovery · 2023Article
- A new class of anti-proliferative activity and apoptotic inducer with molecular docking studies for a novel of 1,3-dithiolo[4,5-RSC advances · 2023Article
- Review
- c-FLIP promotes drug resistance in non-small-cell lung cancer cells via upregulating FoxM1 expression.Acta pharmacologica Sinica · 2022Article
- Targeting apoptosis to manage acquired resistance to third generation EGFR inhibitors.Frontiers of medicine · 2022Review
- Article
- Preclinical Models for Acquired Resistance to Third-Generation EGFR Inhibitors in NSCLC: Functional Studies and Drug Combinations Used to Overcome Resistance.Frontiers in oncology · 2022Review
- Membrane-Associated RING-CH 8 Functions as a Novel PD-L1 E3 Ligase to Mediate PD-L1 Degradation Induced by EGFR Inhibitors.Molecular cancer research : MCR · 2021Article
- LncRNA AC079630.4 expression associated with the progression and prognosis in lung cancer.Aging · 2021Article
- Downregulation of death receptor 4 is tightly associated with positive response of EGFR mutant lung cancer to EGFR-targeted therapy and improved prognosis.Theranostics · 2021Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
The third-generation EGFR inhibitor, osimertinib (AZD9291), selectively and irreversibly inhibits EGFR activating and T790 M mutants while sparing wild-type EGFR. Osimertinib is now an approved drug for non-small cell lung cancer (NSCLC) patients with activating EGFR mutations (first-line) or those who have become resistant to 1st generation EGFR inhibitors through the T790 M mutation (second-line). Unfortunately, all patients eventually relapse and develop resistance to osimertinib. Hence, it is essential to fully understand the biology underlying the development of resistance to osimertinib in order to improve its therapeutic efficacy and overcome resistance. Cellular FLICE-inhibitory protein (c-FLIP) is a truncated form of caspase-8 and functions as a key inhibitor of the extrinsic apoptotic pathway. The current study has demonstrated that osimertinib reduces c-FLIP levels via facilitating its degradation and enhances apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) primarily in NSCLC with activating EGFR mutations. Moreover, modulation of c-FLIP expression levels, to some degree, also alters the sensitivities of EGFR mutant NSCLC cells to undergo osimertinib-induced apoptosis, suggesting that c-FLIP suppression is an important event contributing to the antitumor activity of osimertinib against EGFR mutant NSCLC.
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.