2024 World Conference on Lung Cancer (WCLC) - ePosters-EP.12A.10 Multi-Omics Uncovers Signatures Associated with Resistance to Osimertinib in EGFR-Mutant Non-Small Cell Lung Cancer Patients

EP.12A.10 Multi-Omics Uncovers Signatures Associated with Resistance to Osimertinib in EGFR-Mutant Non-Small Cell Lung Cancer Patients

Back to course

Pdf Summary

The study investigates osimertinib's effectiveness in first-line treatment for non-small cell lung cancer (NSCLC) patients with EGFR mutations. The aim is to determine if certain RNA and protein indicators can predict acquired resistance to osimertinib by analyzing longitudinal plasma samples from patients during the baseline and disease progression.<br /><br />Key findings highlight the potential of plasma-derived exosomal RNAs and circulating proteins as biomarkers to detect molecular changes suggesting resistance to osimertinib. Detailed plasma profiling of these biomolecules illustrates the complex involvement of various RNA and protein species that shape the resistance landscape in osimertinib-treated NSCLC.<br /><br />Researchers used multi-omics approaches for thorough profiling. Figures in the study support the findings, with principal component analysis (PCA) and volcano plots helping visualize protein expression differences at baseline compared to disease progression. For the RNA landscape, PCA and heatmaps show gene expression changes over time, while pathway enrichment analysis identifies key pathways involved in developing resistance.<br /><br />Ultimately, expression analyses were backed by proteome and transcriptome data distinguishing between osimertinib-sensitive and -resistant NSCLC cell lines, validating findings with RT-qPCR for relative expression measurement. The research offers insights into potential diagnostic tools and therapeutic targets for predicting and overcoming osimertinib resistance in EGFR-mutant NSCLC patients, providing a more personalized treatment approach.<br /><br />The study was conducted by researchers from the Karolinska Institutet in Stockholm, in collaboration with Oslo University Hospital, highlighting significant contributions to understanding drug resistance mechanisms in targeted cancer therapies.

Asset Subtitle

Per Hydbring

Meta Tag

Speaker Per Hydbring

Topic Metastatic Non-small Cell Lung Cancer – Targeted Therapy

Keywords

osimertinib

NSCLC

EGFR mutations

acquired resistance

exosomal RNAs

circulating proteins

multi-omics

biomarkers

plasma profiling

drug resistance