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Poster Presentations
Day 1, June 22（Sun.）
Room P (Maesato East, Foyer, Ocean Wing)
- 1P-PM-13
Membrane Proteomic Analysis Revealed Resistant Mechanisms of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors In Lung Cancer Cells
(1NTU, 2TMU)
oYu Teng Jheng1, Chia Li Han2
The advent of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) has significantly advanced the treatment of non-small cell lung cancer (NSCLC) harboring EGFR mutations. However, drug resistance emerges with induction of secondary mutations in EGFR and other off-target mechanisms, contributing to cancer relapse. To explore resistance mechanisms, we employed membrane proteome analysis by data-independent acquisition mass spectrometry as well as EGFR complexes analysis by affinity purification mass spectrometry with multiple enzymatic digestion on gefitinib- and osimertinib-treated H1975 lung cancer cells harboring L858R and T790M mutations. Our findings indicate that gefitinib treatment reduces EGFR expression more markedly than osimertinib. Gefitinib alters pathways related to carbohydrate metabolism, transmembrane transport, and antigen presentation, while osimertinib primarily affects proton transport and MHC class I-mediated antigen presentation. Notably, SERPINH1 is upregulated, and CTNNA1 is downregulated with gefitinib; HSPB1 and CTSD are upregulated, whereas ENO1, VIM, CLTC, and CFL1 are downregulated with osimertinib. Both treatments upregulate MT-CO2 and TUBA1A. These results suggest that resistance mechanisms extend beyond specific EGFR mutations, involving metabolic reprogramming and antigen presentation alterations. These insights are crucial for developing strategies to overcome TKI resistance in NSCLC.