2025 Volume 7 Pages 9-
The T790M secondary mutation in epidermal growth factor receptor (EGFR) drives resistance to tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC), posing a significant therapeutic challenge. To investigate the molecular basis linking acquired mutation to TKI resistance, affinity purification coupled with mass spectrometry (AP-MS) was used to explore the EGFR protein-protein interaction (PPI) networks (interactomes) in TKI-sensitive versus TKI-resistant patient-derived NSCLC cells, which harbored different EGFR mutants. High-resolution mass spectrometry–based proteomics analysis offers robust insights into the PPI network associated with the secondary T790M mutation.