Table 2.
Ferroptosis sensitizing combinatorial strategies tested in cancer models in vivo
| Ferroptosis combinatorial strategies | Mechanism | Cancer model(s) | Ref | |
|---|---|---|---|---|
| Cisplatin | Erastin | Inhibition of GSH synthesis, induction of ferritinophagy | Ovarian cancer | (134) |
| Sulfasalazine | GSH depletion, lipid ROS accumulation | Head and Neck Cancer | (135) | |
| BSO | GOT1 deletion | GSH depletion | Pancreatic cancer | (47) |
| IKE | Dichloroacetate | System xC− and PDK4 inhibition | Pancreatic cancer | (63) |
| Dihydroartemisinin | GPX4 deletion | Degradation of ferritin, lipid ROS | Lung cancer | (130) |
| Cisplatin | Degradation of GPX4, accumulation of iron | Pancreatic cancer | (136) | |
| Artesunate | GRP78 deletion | Lipid peroxidation | Pancreatic cancer | (128) |
| Brequinar | GPX4 silencing | Lipid peroxidation | Fibrosarcoma | (60) |
| Sulfasalazine | ||||
| Rapamycin | GPX4 deletion | Lipid peroxidation | Pancreatic cancer | (137) |
| Sorafenib | Sigma-1 receptor depletion | Lipid peroxidation, Fe2+ elevation | Hepatocellular carcinoma | (138) |
| Sulfasalazine | Pioglitazone | xCT inhibition and Fe2+ elevation | Head and Neck cancer | (126) |
| Metformin | Fe2+ elevation, lipid ROS | Breast cancer | (139) | |
| Sorafenib | Ferritinophagy, xCT inhibition | Pancreatic cancer | (140) | |
| IFNγ | xCT suppression, lipid ROS | Fibrosarcoma | (86) | |
| Oxyfedrine | Sulfasalazine | GSH depletion, 4-HNE accumulation | Colon cancer | (127) |
| Radiation therapy | IKE, Sorafenib | Lipid peroxidation, decreased GSH | Fibrosarcoma | (116) |
| Sulfasalazine | Decreased GSH | Melanoma, Lung Cancer | (114, 115, 141) | |
| Cyst(e)inase, Anti-CTLA4, Anti- PD-L1 | IFN release, xCT suppression, ATM activation, lipid peroxidation | Melanoma | (113) | |
| X-ray irradiation | Erastin | Decreased GPX4 and GSH | Non-small cell lung cancer (NSCLC) | (142) |
| Immune checkpoint blockade: anti-PD-L1, anti-CTLA4 | Cyst(e)inase | xCT suppression, cysteine depletion, lipid ROS | Melanoma | (86) |
Abbreviations: 4-HNE, 4-Hydroxynonenal; ATM, ataxia-telangiectasia mutated; BSO, buthionine sulfoximine; CTLA4, cytotoxic T-lymphocyte-associated protein 4; GOT1, glutamate oxaloacetate transaminase 1; GPX4, glutathione peroxidase 4; GSH, glutathione; IFNγ, interferon gamma; IKE, imidazole ketone erastin; PD-L1, programmed death-ligand 1; PDK4, pyruvate dehydrogenase kinase 4; ROS, reactive oxygen species.