ArticleMolecular medicine (Cambridge, Mass.)2020
Primary resistance to first-generation EGFR-TKIs induced by MDM2 amplification in NSCLC.
Article in Molecular medicine (Cambridge, Mass.), 2020. 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.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- Optimal Treatments for NSCLC Patients Harboring Primary or AcquiredTechnology in cancer research & treatmentPooled it
- Icotinib, an EGFR tyrosine kinase inhibitor, as adjuvant therapy for patients with stage IIA-IIIA EGFR-mutant non-small-cell lung adenocarcinoma: a multicenter, open-label, single-arm, phase II study (ICAPE).Investigational new drugs · 2023Trial
- Silencing of NUP62 overcomes osimertinib resistance via ubiquitination of survivin in non-small cell lung cancer cells.British journal of cancer · 2026Article
- Exosomal circ_0050688 Shapes a Chemoresistant Microenvironment by Driving Spatial Resistance Spreading in Glioblastoma via the MDM2 Pathway.Biomolecules · 2026Article
- cGAS Downregulation Contributes to EGFR-TKI Resistance in NSCLC through the p-Nrf2-SIRT3-ROS/Ferroptosis Axis.Oncology research · 2026Article
- A cohort-based multi-omics identifies nuclear translocation of eIF5B /PD-L1/CD44 complex as the target to overcome Osimertinib resistance of ARID1A-deficient lung adenocarcinoma.Experimental hematology & oncology · 2025Article
- Targeting MDM2, RAS, and PCNA for cancer targeted therapy: pan-cancer approaches vs. cancer-specific strategies.Frontiers in pharmacology · 2025Review
- USP22 promotes gefitinib resistance and inhibits ferroptosis in non-small cell lung cancer by deubiquitination of MDM2.Thoracic cancer · 2024Article
- Profiling Cell-Free DNA from Malignant Pleural Effusion for Oncogenic Driver Mutations in Patients with Treatment-Naive Stage IV Adenocarcinoma: A Multicenter Prospective Study.Molecular diagnosis & therapy · 2024Article
- Advances of E3 ligases in lung cancer.Biochemistry and biophysics reports · 2024Review
- MDM2 Inhibitors for Cancer Therapy: The Past, Present, and Future.Pharmacological reviews · 2024Review
- Revealing the active ingredients and mechanism ofHeliyon · 2024Article
- Targeting MDM2 in malignancies is a promising strategy for overcoming resistance to anticancer immunotherapy.Journal of biomedical science · 2024Review
- Pyrrolo[2,3-D]Pyrimidines as EGFR and VEGFR Kinase Inhibitors: A Comprehensive SAR Review.Current medicinal chemistry · 2024Review
- Aberrant m5C hypermethylation mediates intrinsic resistance to gefitinib through NSUN2/YBX1/QSOX1 axis in EGFR-mutant non-small-cell lung cancer.Molecular cancer · 2023Article
- Drug Discovery Targeting Post-Translational Modifications in Response to DNA Damages Induced by Space Radiation.International journal of molecular sciences · 2023Review
- Prognostic value of cell-free DNA in cerebrospinal fluid from lung cancer patients with brain metastases during radiotherapy.Radiation oncology (London, England) · 2023Article
- Xprediction: Explainable EGFR-TKIs response prediction based on drug sensitivity specific gene networks.PloS one · 2022Article
- Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionTargeted therapy for NSCLC is rapidly evolving. EGFR-TKIs benefit NSCLC patients with sensitive EGFR mutations and significantly prolong survival. However, 20-30% of patients demonstrate primary resistance to EGFR-TKIs, which leads to the failure of EGFR-TKI treatment. The mechanisms of primary resistance to EGFR-TKIs require further study.
methodsTargeted sequencing was used for the detection of genomic alterations among patients in our center. Regular cell culture and transfection with plasmids were used to establish NSCLC cell lines over-expressing MDM2 and vector control. We used the MTT assays to calculate the inhibition rate after exposure to erlotinib. Available datasets were used to determine the role of MDM2 in the prognosis of NSCLC.
resultsFour patients harboring concurrent sensitive EGFR mutations and MDM2 amplifications demonstrated insensitivity to EGFR-TKIs in our center. In vitro experiments suggested that MDM2 amplification induces primary resistance to erlotinib. Over-expressed MDM2 elevated the IC50 value of erlotinib in HCC2279 line and reduced the inhibition rate. In addition, MDM2 amplification predicted a poor prognosis in NSCLC patients and was associated with a short PFS in those treated with EGFR-TKIs. The ERBB2 pathway was identified as a potential pathway activated by MDM2 amplification could be the focus of further research.
conclusionMDM2 amplification induces the primary resistance to EGFR-TKIs and predicts poor prognosis in NSCLC patients. MDM2 may serve as a novel biomarker and treatment target for NSCLC. Further studies are needed to confirm the mechanism by which amplified MDM2 leads to primary resistance to EGFR-TKIs.
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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.