Table 2.
The synergistic effect of anti-tumor therapy together with ferroptosis inducers.
| Treatment | Drugs | Drugs | Target | Cancer type | Mechanism | References |
|---|---|---|---|---|---|---|
| Chemotherapy | Cisplatin | RSL3 | GPX4 | Lung cancer | Inhibition of GPX4 via RSL3 could enhance the anticancer effect of cisplatin | (17) |
| Erastin | GSH-GPXs | NSCLC | Cisplatin can deplete the GSH and inactivate the GPXs together with erastin | (18) | ||
| Colorectal cancer | ||||||
| Erastin | System Xc- | PDAC | Both SLC7A11-KO cell lines exhibit amino acid stress with induction of ATF4 and cell death | (30) | ||
| Erastin | System Xc- | Ovarian cancer | Erastin can inhibit system Xc- and potentiate the cytotoxic effects of cisplatin to eradicate tumor cells | (31) | ||
| Erastin/SAHA | ROS | NSCLC | SAHA and erastin, the inducers of ROS-mediated cell death, strongly enhanced the effect of cisplatin in WT EGFR cells | (32) | ||
| Gemcitabine | Erastin | System Xc- | PDAC | Both SLC7A11-KO cell lines exhibit amino acid stress with induction of ATF4 and cell death | (30) | |
| Paclitaxel | RSL3 | System Xc- | HPSCC | The combination therapy upregulates mtp53 expression, which mediated transcriptional regulation of SLC7A11 | (33) | |
| TMZ | Erastin | System Xc- | Glioma | Erastin sensitizes glioblastoma cells to TMZ by restraining SLC7A11 and CTH function | (26) | |
| ALZ003 | GPX4 | Glioblastoma | AR suppressor ALZ003 can inhibit TMZ-resistant glioblastoma through inhibiting GPX4 | (34) | ||
| Artesunate | Trigonelline | NRF2 | Head and neck cancer | NRF2 inhibitor trigonelline can induce lipid peroxide accumulation | (16) | |
| Cytarabine/ara-C and Doxorubicin /adriamycin | Erastin | – | Acute myeloid leukemia | JNK and p38 cooperatively participate in cell death induced by erastin in HL-60 cells | (35) | |
| SSZ | CN-A and PL | – | Pancreatic cancer | PL markedly depletes GSH and may inhibit GPX activity | (36) | |
| PL | – | Pancreatic cancer | PL markedly depletes GSH and may inhibit GPX activity | (36) | ||
| Target therapy | Lapatinib | Siramesine | Fe | Breast cancer | The combination therapy induces ferroptosis by elevating the intracellular iron level | (37) |
| Lapatinib | Siramesine | Fe | Breast cancer | The combination therapy induces ferroptosis by elevating the intracellular iron level | (37) | |
| Lapatinib | Siramesine | Fe, Lipid peroxidation | Glioma | The combination therapy induces ferroptosis by elevating the intracellular iron level | (38) | |
| Lung adenocarcinoma | ||||||
| Sorafenib | X1 | Lipid peroxidation | HCC | The combination therapy increases oxidative stress and mitochondrial dysfunction through activation of JNKs | (39) | |
| Sorafenib | Trigonelline | NRF2 | HCC | NRF2 inhibitor trigonelline can induce lipid peroxide accumulation | (27) | |
| Radiotherapy | X-ray irradiation | Erastin | GPX4 | Cervical adenocarcinom | Erastin induces ferroptosis and decreases the expression levels of GSH and GPX4 protein | (40) |
| Lung adenocarcinoma | ||||||
| SSZ | System Xc- | Melanoma | SSZ decreases the intratumoral level of GSH, leading to enhanced susceptibility to radiation therapy | (41) | ||
| Laser irradiation | Gallic acid | GPX4, Lipid peroxidation | Breast cancer | Using pre-red laser irradiation could improve anticancer effects of gallic acid through decreasing GPX4 activity | (42) | |
| Melanoma | ||||||
| Microbeam irradiation | IKE/RSL3/sorafinib | System Xc-, GPX4 | Sarcoma | System xc- or GPX4 inhibitors synergize with cytoplasmic irradiation to induce ferroptosis by enhancing cytoplasmic lipid peroxidation | (43) | |
| Glioblastoma | ||||||
| Lung cancer | ||||||
| Gamma knife radiosurgery | SSZ | System Xc- | Glioblastomas | SSZ treatment significantly reduced cystine uptake and GSH levels, and significantly increased the levels of ROS | (44) | |
| γ-radiation | Erastin | System Xc- | Breast cancer | System Xc- enhanced GSH synthesis. GSH is used to control ROS, which are therapeutic effectors of radiation therapy | (45) | |
| Ionizing radiation | Anti-PD-L1/Anti-CTLA4 mAb | System Xc- | Sarcoma | ATM activated by radiotherapy and IFN derived from activated CD8+ T cells synergistically inhibited the expression of SLC7A11 | (46) | |
| Melanoma | ||||||
| Ovarian cancer | ||||||
| Other therapy | Statins | Erlotinib/Gefitinib | GPX4 | Lung cancer | Statins block the synthesis of GPX4 | (47) |
| Acetaminophen | Erastin | Iron, Lipid peroxidation | NSCLC | Acetaminophen enhances the sensitivity of erastin-induced ferroptosis by regulating the NRF2/HO-1 signaling pathway | (48) | |
| Bromelain | Erastin | ACSL4 | Colorectal cancer | Bromelain induces ROS-induced ferroptosis via the modulation of ACSL4 | (49) | |
| Metadherin | ML162 /ML210 | SLC3A2, GPX4 | Endometrial cancer | MTDH can inhibit the activities of GPX4 and SLC3A2 | (50) | |
| Erastin | ACSL4 | Breast cancer | Bromelain induces ROS-induced ferroptosis in Kras mutant Colorectal cancer cells via ACSL4 | |||
| SCD1 inhibitors | RSL3/Erastin PEITC |
Lipid peroxidation ROS |
Ovarian Cancer | Stearoyl-CoA desaturase 1 inhibitors decrease an endogenous membrane antioxidant CoQ10 CN-A and PEITC synergistically trigger ROS accumulation |
(51) | |
| CN-A | Pancreatic cancer | (52) | ||||
| PL | ROS, GSH, GPX | Pancreatic cancer | PL markedly depletes GSH and may inhibit GPX activity | (36) | ||
| SSZ and PL | ROS | Pancreatic cancer | PL markedly depletes GSH and may inhibit GPX activity | (36) | ||
| Immunotherapy | Dichloroacetate | Albiziabioside A | GPX4 | Breast cancer | AlbA-DCA can inhibit GPX4 and eliminate M2-TAMs to suppress tumor progression | (53) |
| SSZ and PL | Melonoma | PL markedly depleted GSH and may inhibit GPX activity | ||||
| Pa | Ti | – | Melanoma | Pa and Ti cooperately polarize M2-TAMs into M1-TAMs and promote the Fenton reaction with Fe ions discharged from magnetic nanoclusters | (54) | |
| Breast cancer | ||||||
| Oxygen-boosted PDT | Ferroptosis inducers | – | Breast cancer | PDT induces lymphocytes infiltration in the tumor site and stimulates the secretion of IFN-γ | (55) |
PDAC, Pancreatic ductal adenocarcinoma; HCC, Hepatocarcinoma; CN-A, Cotylenin A; PEITC, Phenethyl isothiocyanate; PL, Piperlongumine; PDT, Photodynamic therapy; Pa, PD-1 antibody; Ti, TGF-β inhibitor; IKE, Imidazole ketone erastin; HPSCC, Hypopharyngeal squamous carcinoma; SSZ, Sulfasalazine; TMZ, Temozolomide; AR, Androgen receptor; WT, wild-type; EGFR, Epidermal growth factor receptor; TKI, tyrosine kinase inhibitor; PFS, Progression-free survival; NSCLC, Non-small cell lung cancer; TAM, Tumor-associated macrophage; ATM, Ataxia-Telangiectasia mutated gene; CTH, cystathionine γ-lyase.