Table 1.
Therapeutic approaches, their targets in XP, level of evidence, and grade of recommendation
| Approach | Target | References | *Level of evidence | Grade of recommendation |
|---|---|---|---|---|
| Current approaches | ||||
| 1. Sun avoidance | UVB spectrum of UV irradiation forms cyclobutane pyrimidine dimers (CPDs) and initiates skin cancer. It also causes immunosuppression which allows transformed cells to be replicated complicating the situation. Avoidance of sun provides protection of UV radiation delaying cancer manifestation in XP patients. | [6,8,11,15] | 1 | Strong evidence |
| 2. Tumor ablation, dermabrasion, and chemical peels | Surgical removal of cancerous lesions prevents the spread of cancer cells. Dermabrasion and chemical abrasion were used earlier as a prophylactic approach. | [20,21,22,23] | 3 | Weak evidence |
| 3. Laser and photodynamic therapy (PDT) | Laser treatments reduce the occurrence of nonmelanoma skin cancers and PTD uses photosensitizing agent that after light activation destroy cancer cells. | [5,23] | 3 | Weak evidence |
| 4. Retinoids | Prevents the formation of carcineous carcinoma in XP patient exerting their anticancer effect through their pro-extracellular matrix activity, the maintenance of stem cells (having mutagenic DNA lesion) and/or the inhibition of matrix degrading enzymes such as matrix metalloproteinases. | [24,25,26,27,28,29,30] | 1 | Strong evidence |
| 5. 5-Fluorouracil | Inhibits all production of thymidine triphosphate (TTP) from uracil, resulting cell death through apoptosis. | [31,32] | 3 | Weak evidence |
| 6. T4 endonuclease V | Repair UV-induced DNA lesions restoring normal level of undifferentiated sarcoma | [33] | 2 | Moderate evidence |
| 7. Imiquimod | Improves pigmentation alterations and defects in the skin texture | [34,35] | 4 | Theoretical evidence |
| 8. Photolyase | Involved in light-dependent DNA repair named photoreactivation. | [8] | 2 | Moderate evidence |
| 9. Antioxidants | Reduce oxidative stress, which is considered to cause neurological symptoms in XP patients. | [36] | 2 | Moderate evidence |
| 10. Interferon alpha | It is an immunomodulator and antiproliferative complex, effective against melanomas. | [37] | 4 | Theoretical evidence |
| Futuristic Approaches | ||||
| 11. Oral vismodegib | Inhibits hedgehog pathway | [21] | 4 | Theoretical evidence |
| 12. Immunotherapy | Blocks binding of PD-L1 and boosts immune response against cancer cell | [38,39] | 4 | Theoretical evidence |
| 13. Nicotinamide | Supposed to repress SIRT1 and rescues mitochondrial phenotype | [40,41,42,43] | 3 | Weak evidence |
| 14. Acetohexamide or glimepiride | Supposed to degrade MUTYH, a DNA glycosylase | [44,45] | 5 | Mechanism-based evidence |
| 15. Restricted diet | May increase resistance to stress induced by DNA-damage | [46] | 5 | Mechanism-based evidence |
| 11. Potentials of gene therapy | The transfer of missing/defective genetic materials and corrections by genome edition. | [47,48,49,50] | 5 | Mechanism-based evidence |
*The level of evidence for each therapeutic option are assigned according to “Oxford center of EBM guidelines.”[51]