ArticleCell death & disease2021
Gefitinib initiates sterile inflammation by promoting IL-1β and HMGB1 release via two distinct mechanisms.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 44 citations in OpenAlex.
- DR.DEGMON: self-explainable deep neural network for drug-induced cell viability prediction incorporating differentially expressed genes and gene ontology.BMC medical genomics · 2026Article
- Preclinical evaluation of gefitinib and betulin-loaded surface functionalized liposomes for the treatment of hepatocellular carcinoma via asialoglycoprotein receptor targeting.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Targeted Therapy-Induced Interstitial Lung Disease in NSCLC: Mechanisms, Clinical Signatures, and a Precision Medicine Roadmap.Drug design, development and therapy · 2026Review
- AMPK Limits MNNG-Induced Parthanatos by Inhibiting BH3-Only Protein Bim.International journal of molecular sciences · 2025Article
- Macrophage NLRP3 activation and IL-1β release drive osimertinib-induced antitumor immunity.Journal for immunotherapy of cancer · 2025Article
- The antirheumatic drug sulfasalazine ameliorates acute renal failure (ARF) induced by polymyxin B.The Journal of antibiotics · 2025Article
- Expert consensus on cancer treatment-related lung injury.Journal of thoracic disease · 2025Review
- The Selective 3-MST Inhibitor I3MT-3 Works as a Potent Caspase-1 Inhibitor.International journal of molecular sciences · 2025Article
- Berberine protects against gefitinib-induced liver injury by inhibiting the HMGB1/TLR4/NF-κB pathway.Frontiers in pharmacology · 2025Article
- CXCR1 and CXCR2 Antagonism with G31P Attenuates Chemotherapy-Induced Lung Inflammation and Augments the Gefitinib Therapeutic Response in Lung Cancer.Oncology research · 2025Article
- Involvement of role of HMGB1-NLRP3 pathway in systemic disorders.Frontiers in cell and developmental biology · 2025Review
- Molecular Hydrogen Protects against Various Tissue Injuries from Side Effects of Anticancer Drugs by Reducing Oxidative Stress and Inflammation.Biomedicines · 2024Review
- The E3 Ubiquitin Protein Ligase LINCR Amplifies the TLR-Mediated Signals through Direct Degradation of MKP1.Cells · 2024Article
- NEAT1_1 confers gefitinib resistance in lung adenocarcinoma through promoting AKR1C1-mediated ferroptosis defence.Cell death discovery · 2024Article
- Aggregability of the SQSTM1/p62-based aggresome-like induced structures determines the sensitivity to parthanatos.Cell death discovery · 2024Article
- LLPS of SQSTM1/p62 and NBR1 as outcomes of lysosomal stress response limits cancer cell metastasis.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- PARP1 Activation Induces HMGB1 Secretion Promoting Intestinal Inflammation in Mice and Human Intestinal Organoids.International journal of molecular sciences · 2023Article
- Valsartan prevents gefitinib-induced lung inflammation, oxidative stress, and alteration of plasma metabolites in rats.Saudi journal of biological sciences · 2023Article
- 18β-Glycyrrhetinic Acid AlleviatesInfection and drug resistance · 2023Article
- Evaluation of the potential complication of interstitial lung disease associated with antifibrotic drugs using data from databases reporting spontaneous adverse effects.Clinical and translational science · 2022Article
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Anticancer drug gefitinib causes inflammation-based side effects, such as interstitial pneumonitis. However, its mechanisms remain unknown. Here, we provide evidence that gefitinib elicits pro-inflammatory responses by promoting mature-interleukin-1β (IL-1β) and high-mobility group box 1 (HMGB1) release. Mitochondrial reactive oxygen species (mtROS) driven by gefitinib stimulated the formation of the NLRP3 (NACHT, LRR and PYD-containing protein 3) inflammasome, leading to mature-IL-1β release. Notably, gefitinib also stimulated HMGB1 release, which is, however, not mediated by the NLRP3 inflammasome. On the other hand, gefitinib-driven mtROS promoted the accumulation of γH2AX, a hallmark of DNA damage, leading to the activation of poly (ADP-ribose) polymerase-1 (PARP-1) and subsequent active release of HMGB1. Together our results reveal the potential ability of gefitinib to initiate sterile inflammation via two distinct mechanisms, and identified IL-1β and HMGB1 as key determinants of gefitinib-induced inflammation that may provide insights into gefitinib-induced interstitial pneumonitis.
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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.