KEAP1-NRF2 Pathway as a Novel Therapeutic Target for EGFR-Mutant NSCLC

Abstract

This study elucidates the KEAP1-NRF2 pathway as a potential therapeutic target for EGFR-mutant NSCLC. NRF2 expression was enhanced in gefitinib-resistant cells. NRF2 inhibition with brusatol enhanced osimertinib-induced cell death and potentiated tumor growth inhibition in xenograft model.

Key Findings

• NRF2 is elevated in gefitinib-resistant EGFR-mutant NSCLC cells
• Brusatol causes dose-dependent NRF2 downregulation and cell death
• NRF2 inhibition synergizes with osimertinib
• Establishes NRF2 modulation as strategy to overcome EGFR-TKI resistance

Clinical Significance

Citation

Choi, J.S. et al. (2025). KEAP1-NRF2 in EGFR-Mutant NSCLC. Tuberculosis and Respiratory Diseases.