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Cancer FerroptosisCancer Drug ResistanceTherapeutics

The Nrf2-HMOX1 pathway as a therapeutic target for reversing cisplatin resistance in NSCLC via inhibiting ferroptosis

Cell Death Discovery

Abstract

Cisplatin resistance is a major cause of poor prognosis in NSCLC. This study demonstrates that Nrf2-sensitized cisplatin-resistant cells by enhancing ferroptosis. The Nrf2-HMOX1 pathway mediates anti-ferroptosis; inhibition with ML385 restores cisplatin sensitivity.

Key Findings

  • NRF2 activation confers ferroptosis resistance in cisplatin-resistant NSCLC
  • ML385 restores cisplatin sensitivity by enhancing ferroptosis
  • High NRF2/HMOX1 correlates with poor survival in NSCLC patients
  • Preclinical evidence for combining NRF2 inhibitors with platinum chemotherapy

Clinical Significance

Directly addresses cisplatin resistance in lung cancer. Identifies NRF2-HMOX1 as druggable target with immediate translational potential.

Citation

Zuo, L. et al. (2025). Nrf2-HMOX1 in cisplatin resistance. Cell Death Discovery.

DOI: 10.1038/s41420-025-02564-z