2023 World Conference on Lung Cancer (Posters)-P2.09. Combined Multi-omics Explore the Resistance Mechanism of Third-generation EGFR-TKI BPI-7711

P2.09. Combined Multi-omics Explore the Resistance Mechanism of Third-generation EGFR-TKI BPI-7711 - PDF(Slides)

Pdf Summary

Researchers conducted a study to explore the resistance mechanism of a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) called BPI-7711. They created a stable BPI-7711-resistant cell line called HCC827R and used combined multi-omics analysis to uncover the critical resistance pathway. The results showed that the resistant cell line had enhanced invasion and migration abilities through remodeling the extracellular matrix. The JAK2-STAT3 pathway was identified as a potential regulation pathway in the development of resistance. The researchers suggested that a combination of a STAT3 inhibitor and BPI-7711 could be a potential therapeutic regimen for third-generation EGFR-TKI resistance. <br /><br />In the study, a total of 1983 differential expression genes (DEGs) and 1022 differential expression proteins (DEPs) were identified in the differential analysis between the drug-sensitive and drug-resistant cell lines. Vocalno plots and heatmaps were used to visualize the DEGs and DEPs. The combined multi-omics analysis revealed that invasion, migration, and the epithelial-mesenchymal transition (EMT) related pathways were significantly up-regulated in the drug-resistant cell line. The protein-protein interaction (PPI) network analysis identified STAT3 as a hub protein. Furthermore, the JAK2-STAT3 signaling pathway was found to be significantly up-regulated in the drug-resistant cell line according to KEGG pathway analysis.<br /><br />The study concluded that BPI-7711-resistant cells exhibited increased migration and invasion abilities. The JAK2-STAT3 pathway was potentially involved in the development of drug resistance. The findings suggest that a combination of a STAT3 inhibitor and BPI-7711 could be an effective therapeutic approach for patients with third-generation EGFR-TKI resistance.

Asset Subtitle

Ruyun Gao

Meta Tag

Speaker Ruyun Gao

Topic Metastatic NSCLC: Targeted Therapy - EGFR/HER2

Keywords

epidermal growth factor receptor tyrosine kinase inhibitor

BPI-7711

resistance mechanism

HCC827R

multi-omics analysis

extracellular matrix remodeling

JAK2-STAT3 pathway

third-generation EGFR-TKI resistance

differential expression genes

differential expression proteins