Table 1.
Reactive species-mediated effects of receptor-targeted therapy.
| Target | Drug Name | Implicated ROS | Suggested Mechanism | Putative Redox Biomarkers | References |
|---|---|---|---|---|---|
| VEGFR | Axitinib | Not specified | Not specified | Oxidative DNA damage byproducts | [126] |
| Sunitinib | ↓NO | Increased GSH down regulated NOS |
- | [127,128] | |
| Sorafenib | ↑H2O2, O2−, NO | Mitochondrial dysfunction and GSH depletion | Advanced oxidation protein products | [129] | |
| EGFR | Crizotinib | ↑O2− | Prx upregulation associated with drug resistance | - | [130] |
| Afatinib | Not specified | Oxidative stress associated with drug resistance | - | [131] | |
| Erlotinib | Not specified | Induced ROS-mediated apoptosis | - | [132] | |
| Gefitinib | Not specified | Prx II upregulation associated with drug resistance | - | [133] | |
| HER1/HER2 | Lapatinib | Not specified | Upregulated SOD1/ SOD2 and GSH associated with drug resistance | - | [134] |
| HER2 dimerization | Trastuzumab | Not specified | Increased Trx-1 associated with drug resistance | Restoration of plasma antioxidant activity | [135] |
| PDGFRα, KIT, ABL, CSF-1 receptor | Imatinib | Not specified | ROS-dependent apoptosis | - | [126] |
| BRAF V600E | Vemurafenib | ↑ NO and O2− production | Depolarization of mitochondrial membrane, induced PGC1α | - | [136,137] |
JNK = c-Jun N-terminal kinase; Prx II = peroxiredoxin II; HER = human epidermal growth factor receptor; PDGFR = platelet-derived growth factor receptor; KIT (CD117) = proto-oncogene, receptor tyrosine kinase; ABL = non-receptor tyrosine kinase; CSF-1 = colony-stimulating factor-1; PDGFR = platelet-derived growth factor receptor; EGFR = epidermal growth factor receptor; PGC-1 = peroxisome proliferator-activated receptor-gamma coactivator-1; Trx = thioredoxin; GSH = glutathione; VEGFR = vascular endothelial growth factor receptor. ↓ decreased, ↑ increased.