Table 2.
Clinical or preclinical application of ferroptosis in hepatocellular carcinoma (HCC).
| Treatment | Target | Possible mechanism | Reference |
| DHA | LOXs | By promoting the binding of PEBP1 and 15-LO, and activating LOXs allosterically to induce lipid peroxidation | [30] |
| An LCN2-neutralizing antibody | LCN2 | By targeting the upregulation of LCN2 mediated by loss of LIFR and upregulating Fe2+ and lipid peroxidation levels | [109] |
| Sorafenib | System xc− | By inhibiting system xc− for absorption of cystine, and promoting the depletion of GSH | [123] |
| ART | Ferritin | By inducing ferritinophagy and releasing iron into the cytosol to produce ROS, which can also synergize with sorafenib | [97,98] |
| QSOX1 | NRF2 | By promoting the nuclear endosome transport of EGFR and restraining the activity of NRF2 | [99] |
| A cascaded copper-based nanocatalyst | GSH | By improving the water solubility of sorafenib and increasing the levels of GSH and COX-2 | [100] |
| MMSNs loaded with sorafenib | GSH | By promoting the depletion of GSH and increasing the targeting characteristics of sorafenib, achieving synergism | [102] |
| Co-administration of MIL-101(Fe)@sor NPs with iRGD | GSH; GPX4 | By reducing the levels of GSH and activity of GPX4 | [101] |
| RSL3@O2-ICG NBs | GSH | By promoting the depletion of GSH and damaging mitochondria | [122] |
| DSF/Cu | Iron; NRF2 | By disrupting mitochondrial homeostasis, increasing the iron pool and inhibiting NRF2 pathway for synergizing with sorafenib | [105] |
| Solasonine | GPX4 | By restraining the activity of GPX4 and GSS | [107] |
ART: Artesunate; COX-2: Cyclooxygenase-2; DHA: Dihydroartemisinin; DSF: Disulfiram; EGFR: Epidermal growth factor receptor; GPX4: Glutathione peroxidase 4; GSH: Glutathione; GSS: Glutathione synthetase; ICG: Indocyanine green; LCN2: Lipocalin 2; LIFR: Leukemia inhibitory factor (LIF) receptor subunit alpha; LOXs: Lipoxygenases; MMSNs: Manganese-doped mesoporous silica nanoparticles; NBs: Nanobubbles; NPs: Nanoparticles; NRF2: Nuclear factor erythroid 2-related factor; PEBP1: Phosphatidylethanolamine binding protein 1; QSOX1: Quiescin sulfhydryl oxidase 1; RGD: Tumor-homing motif; ROS: Reactive oxygen species.