TherapeuticsCancer Drug ResistanceCancer Ferroptosis

Targeting the NRF2 pathway to enhance lipid peroxidation: a novel therapeutic strategy in hepatocellular carcinoma

Exploration of Medicine 2025-01-01

Exploration of Medicine contributors

Abstract

Persistent activation of NRF2 in malignant hepatocytes suppresses ferroptosis by restricting lipid peroxidation through GPX4, SLC7A11, and ferritin. Pharmacological strategies including NRF2 inhibitors show synergy with sorafenib.

Key Findings

Persistent NRF2 activation suppresses ferroptosis in HCC
NRF2 inhibitors demonstrate synergy with sorafenib
Future directions include PROTACs for hepatocyte-targeted NRF2 modulation
Biomarker-based patient stratification framework proposed

Clinical Significance

Provides roadmap for NRF2-targeted HCC therapy including next-generation approaches like PROTACs.

Citation

Targeting NRF2 pathway in hepatocellular carcinoma. (2025). Exploration of Medicine.

DOI: 10.37349/emed.2025.1001367