ArticleMedComm2026
Sphingosine-1-Phosphate Receptor 3 Confers Tumor Metastasis in Lung Cancer Resistant to Third-Generation EGFR Inhibitor.
Article in MedComm, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
1 citing paper in PubMed.
- Opportunities and challenges in the development of evolving EGFR inhibitors to overcome EGFR TKIs resistance.Acta pharmacologica Sinica · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The third-generation EGFR tyrosine kinase inhibitor (TKI) osimertinib (AZD9291) has significantly improved the survival in EGFR-mutant lung cancer patients. Our team developed limertinib (ASK120067), a novel third-generation EGFR inhibitor with remarkable antitumor effects, which has been launched in China. Despite initial therapeutic responses, EGFR TKIs-treated patients ultimately experience fatal metastatic recurrence and disease progression. However, the underlying mechanism of driving metastasis remains poorly understood. Here, we aim to investigate the pro-metastatic mechanism following treatment with third-generation EGFR TKIs. Transcriptomics analyses of EGFR TKI-resistant tumor models revealed an aberrant upregulation of S1PR3, which conferred enhanced metastatic potential to lung cancer. S1PR3 inhibition dramatically reduced metastasis in resistant cells, while its overexpression potentiated metastatic abilities in parental cells. Notably, S1PR3 was highly enriched in clinical samples with AZD9291 resistance and correlates with poor prognosis. Mechanistically, we found that S1PR3 upregulated RAC1-GTP expression to activate PAK1, thereby promoting epithelial-mesenchymal transition (EMT) and enhancing metastatic capacity of resistant cells. Further studies identified that the overexpression of fibroblast growth factor receptor 1 (FGFR1) increased S1PR3 expression through signal transducer and activator of transcription 4 (STAT4) to promote the emergence of metastatic-resistant cells. Importantly, targeting S1PR3 or FGFR1 blocks metastasis in EGFR TKI-resistant models.
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Registered trials
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