Complementary modes of resistance to <i>EGFR</i> TKI in lung adenocarcinoma through MAPK activation and cellular plasticity.

ABSTRACT: EGFR-mutant lung adenocarcinoma (LUAD) represents 20% of all non-small cell lung carcinomas, with most patients presenting with incurable metastatic disease. Treatment with mutant-selective EGFR tyrosine kinase inhibitors (TKIs) results in initial tumor reduction, yet nearly all patients eventually relapse. The mechanisms driving drug resistance are incompletely understood, creating significant barriers to curing metastatic disease. We integrated clinical genomic and single-nuclei RNA (snRNA) sequencing from a cohort of 62 EGFR-mutant LUAD patients treated with the third generation EGFR TKI, osimertinib, and compared treatment-naïve (TN), minimal residual disease (MRD), and progressive disease (PD) tumors. We found that disease progression is associated with a m

SUBMITTER: Zatzman M 

PROVIDER: S-EPMC12248098 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature