WCLC 2025 - Posters & ePosters-EP.12.26 Multi-Omics Decipher the Molecular Landscape of EGFR+ Non-Small Cell Lung Cancer Patients Following Osimertinib Treatment

EP.12.26 Multi-Omics Decipher the Molecular Landscape of EGFR+ Non-Small Cell Lung Cancer Patients Following Osimertinib Treatment

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This study investigates the molecular mechanisms underlying acquired resistance to osimertinib, a first-line treatment for non-small cell lung cancer (NSCLC) patients with activating EGFR mutations. By longitudinally profiling circulating RNAs and proteins from plasma samples collected at baseline and at disease progression, the researchers aimed to identify biomarkers indicative of resistance development.<br /><br />Using multi-omics approaches, including transcriptome and proteome analyses of plasma-derived exosomal content and circulating proteins, the study characterized distinct molecular phenotypes associated with osimertinib refractoriness. Principal component analyses (PCA) and volcano plots highlighted significant differences in gene and protein expression between baseline and progression samples. Heatmaps further delineated the top differentially expressed genes, underscoring a dynamic shift in the molecular landscape as resistance emerges.<br /><br />Pathway enrichment analyses revealed that several RNA and protein species contribute to this evolving resistance phenotype, indicating complex biological processes are involved. Additionally, comparisons of candidate gene expression in osimertinib-sensitive versus resistant NSCLC cell lines validated some findings at the cellular level via RT-qPCR.<br /><br />Overall, the results demonstrate that plasma-derived exosomal RNAs and circulating proteins serve as accessible biomarkers for monitoring molecular changes during osimertinib treatment, potentially enabling early detection of resistance. This longitudinal molecular profiling extends understanding of the diverse mechanisms driving osimertinib resistance, offering pathways for improved therapeutic strategies and patient management in EGFR-mutant NSCLC.

Asset Subtitle

Per Hydbring

Meta Tag

Speaker Per Hydbring

Topic Metastatic Non-small Cell Lung Cancer – Targeted Therapy

Keywords

osimertinib resistance

non-small cell lung cancer

EGFR mutations

circulating RNAs

plasma proteomics

exosomal biomarkers

multi-omics analysis

transcriptome profiling

proteome analysis

longitudinal molecular profiling