ArticleMolecular medicine reports2021
Inhibition of Bcl-2 and Bcl-xL overcomes the resistance to the third-generation EGFR tyrosine kinase inhibitor osimertinib in non-small cell lung cancer.
Article in Molecular medicine reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 29 citations in OpenAlex.
- BCL-2/BCL-xL inhibitor pelcitoclax with osimertinib forJournal for immunotherapy of cancer · 2026Article
- Osimertinib Resistance in EGFR-Mutated Non-Small Cell Lung Cancer: Mechanisms and Therapeutic Strategies.MedComm · 2026Review
- Traditional Chinese medicine reprograms the tumor microenvironment to overcome EGFR-TKI resistance: mechanisms and therapeutic perspectives.Frontiers in pharmacology · 2026Review
- The Managed Acquisition of Chemoresistance as an Informative Tool for Tumor Research.International journal of molecular sciences · 2025Review
- A novel mesenchymal epithelial transition (MET) inhibitor, CB538, relieves acquired resistance inTranslational cancer research · 2025Article
- Unraveling the triad of hypoxia, cancer cell stemness, and drug resistance.Journal of hematology & oncology · 2025Review
- Repurposing of c-MET Inhibitor Tivantinib Inhibits Pediatric Neuroblastoma Cellular Growth.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Drug tolerant persister cell plasticity in cancer: A revolutionary strategy for more effective anticancer therapies.Signal transduction and targeted therapy · 2024Review
- Integrative single-cell RNA-seq and spatial transcriptomics analyses reveal diverse apoptosis-related gene expression profiles in EGFR-mutated lung cancer.Cell death & disease · 2024Article
- Targeting of drug-tolerant persister cells as an approach to counter drug resistance in non-small cell lung cancer.Lung cancer (Amsterdam, Netherlands) · 2024Review
- The drug efficacy testing in 3D cultures platform identifies effective drugs for ovarian cancer patients.NPJ precision oncology · 2023Article
- Osimertinib is a dual inhibitor of hepatocellular carcinoma and angiogenesis in an EGFR-independent manner, and synergizes with venetoclax.Journal of cancer research and clinical oncology · 2023Article
- Adaptive resistance to lorlatinib via EGFR signaling in ALK-rearranged lung cancer.NPJ precision oncology · 2023Article
- Article
- Targeting apoptosis to manage acquired resistance to third generation EGFR inhibitors.Frontiers of medicine · 2022Review
- Specific Targeting of Antiapoptotic Bcl-2 Proteins as a Radiosensitizing Approach in Solid Tumors.International journal of molecular sciences · 2022Article
- Overcoming the acquired resistance to gefitinib in lung cancer brain metastasis in vitro and in vivo.Archives of toxicology · 2021Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have demonstrated significant benefits to patients with non‑small cell lung cancer (NSCLC) harboring EGFR‑activating mutations; however, acquired resistance limits their long‑term efficacy. Therefore, it remains an urgent requirement to discover the underlying mechanisms and investigate novel therapeutic strategies for overcoming the resistance to EGFR TKIs. The present study aimed to determine the mechanism underlying the resistance of NSCLC cells to osimertinib, a third‑generation EGFR tyrosine kinase inhibitor, the osimertinib‑resistant NSCLC cell sub‑line HCC827/OR was established in the present study. It was found that the expression levels of Bcl‑2 and Bcl‑xL were significantly upregulated in resistant cells compared with sensitive cells. Furthermore, the suppression of Bcl‑2 and Bcl‑xL through small interfering RNA‑mediated gene knockdown or using a small molecule specific inhibitor ABT‑263 re‑sensitized HCC827/OR cells to osimertinib treatment. Moreover, the combined treatment of HCC827/OR cells with ABT‑263 and osimertinib enhanced the rate of cell apoptosis through the mitochondrial apoptotic pathway. Finally, ABT‑263 was able to overcome the resistance of osimertinib in xenograft tumor models. In conclusion, these findings may provide an improved concept for the development of a novel combined therapeutic strategy for the treatment of NSCLC resistance to EGFR TKIs.
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