ArticleProceedings of the National Academy of Sciences of the United States of America2024
Increased expression of SSEA-4 on TKI-resistant non-small cell lung cancer with EGFR-T790M mutation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 14 citations in OpenAlex.
- Drug resistance to antibody-drug conjugates: mechanisms, challenges, and perspectives.Cancer biology & medicine · 2026Review
- Improving the efficacy of anti-SSEA4 antibody in pancreatic cancer immunotherapy with glyco-optimization and immune checkpoint blockade.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Chemical and Enzymatic Synthesis of DisialylGb5 and Other Sialosides for Glycan Array Assembly and Evaluation of Siglec-Mediated Immune Checkpoint Inhibition.Molecules (Basel, Switzerland) · 2025Article
- Recurring cycles of deprivation of serum and migration in confined spaces augments ganglioside SSEA-4 expression, boosting clonogenicity and cisplatin resistance in TNBC cell line.Scientific reports · 2025Article
- Structure-Based Mechanism and Specificity of Human Galactosyltransferase β3GalT5.Journal of the American Chemical Society · 2025Article
- Expression of Human β3GalT5-1 in Insect Cells as Active Glycoforms for the Efficient Synthesis of Cancer-Associated Globo-Series Glycans.Journal of the American Chemical Society · 2025Article
- MUC1 expression is associated with ST3GAL2 and negatively correlated with the androgen receptor in castration-resistant prostate cancer.Glycoconjugate journal · 2024Article
- Integrating network pharmacology and computational biology to propose Yiqi Sanjie formula's mechanisms in treating NSCLC: molecular docking, ADMET, and molecular dynamics simulation.Translational cancer research · 2024Article
- Identification and validation of GIMAP family genes as immune-related prognostic biomarkers in lung adenocarcinoma.Heliyon · 2024Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
Non-small cell lung cancer (NSCLC), a major life-threatening disease accounting for 85% of all lung cancer cases, has been treated with tyrosine kinase inhibitors (TKIs), but often resulted in drug resistance, and approximately 60% of TKI-resistant cases are due to acquired secondary (epithelial growth factor receptor) EGFR-T790M mutation. To identify alternative targets for TKI-resistant NSCLC with EGFR-T790M mutation, we found that the three globo-series glycosphingolipids are increasingly expressed on this type of NSCLC cell lines, and among them, the increase of stage-specific embryonic antigen-4 (SSEA-4) expression is the most significant. Compared to TKI-sensitive cell lines, SSEA-4 and the key enzyme β3GalT5 responsible for the synthesis of SSEA3 are more expressed in TKI-resistant NSCLC cell lines with EGFR-T790M mutation, and the expression levels strongly correlate with poor survival in patients with EGFR mutation. In addition, we demonstrated that a SSEA-4 targeted monoclonal antibody, especially the homogeneous glycoform with well-defined Fc glycan designed to improve effective functions, is highly effective against this subpopulation of NSCLC in cell-based and animal studies. These findings provide a direction for the prediction of tumor recurrence and treatment of TKI-resistant NSCLC with EGFR-T790M mutation.
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