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(Abstract)

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This abstract discusses a study that investigated the resistance mechanism of a novel third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) called BPI-7711 in non-small cell lung cancer (NSCLC) patients. Despite the efficacy of EGFR-TKIs in NSCLC treatment, patients often develop resistance. The study aimed to uncover the resistance pathways and find potential approaches to counteract it.<br /><br />The researchers constructed a cell line resistant to BPI-7711 and conducted a combined multi-omics analysis, including transcriptomics and proteomics. They identified differential expression genes and proteins between the resistant and non-resistant cell lines. The analysis revealed significant up-regulation of invasion, migration, and the epithelial-mesenchymal transition (EMT) pathways in the resistant cell line. They also identified STAT3 as a hub protein in the protein-protein interaction network, with the JAK2-STAT3 signaling pathway being up-regulated in the resistant cells.<br /><br />Further experiments demonstrated that the migration and invasion ability of the resistant cell line was significantly enhanced compared to the non-resistant line. However, a combination of a STAT3 inhibitor (AG490) and BPI-7711 effectively inhibited the invasion and migration ability of the resistant cells and overcame drug resistance in both in vitro and in vivo models.<br /><br />Overall, the study suggests that the JAK2-STAT3 pathway plays a crucial role in the resistance mechanism of BPI-7711. It promotes EMT and enhances invasion and migration ability by remodeling the extracellular matrix. The researchers propose that a STAT3 inhibitor could be a potential therapeutic approach to counter third-generation EGFR-TKI resistance.<br /><br />Keywords: EGFR-TKI, Resistance, NSCLC<br /><br />This research falls under Track 12: Metastatic Non-small Cell Lung Cancer - Targeted Therapy at the WCLC 2023 conference.

Asset Subtitle

Ruyun Gao

Meta Tag

Speaker Ruyun Gao

Topic Metastatic NSCLC: Targeted Therapy - EGFR/HER2

Keywords

EGFR-TKI

BPI-7711

NSCLC

resistance mechanism

invasion

migration

EMT

STAT3

JAK2-STAT3 signaling pathway

drug resistance

NSCLC patients

EGFR-TKI resistance