Table 1.
Summary of possible alterations affecting PpIX levels in cancer cells and their translational impact
| Possible alterations | Effect on PpIX levels | Translational impact | Citation |
|---|---|---|---|
| Altered haem synthesis | |||
| Altered flux of haem synthesis intermediates | ↑ | Altering activity of transporters to maximise PpIX production (includes 5-ALA uptake, influx of PpIX precursors, efflux of PpIX, iron transporters) | 12– 15, 18, 21, 23 |
| Increased CPOX expression/activity | ↑ | Pre-treatment with adjuvants (5-fluorouracil, methotrexate, vitamin D3) | 24– 27 |
| Reduced FECH expression/activity | ↑ | Targeting FECH activity at the tumour site (FECH inhibition, iron chelators, reducing influx of iron, kinase inhibitors, nitric oxide donors, Frataxin inhibition) | 12, 14, 28– 31, 37, 40, 41, 44, 45, 48, 49 |
| Tumour environment | |||
| Hypoxia | ↓ | Increasing oxygen levels at the tumour site (HIF-1 inhibition, nanoparticles) | 61, 62 |
| Altered metabolism | |||
| Altered glucose metabolism | ↑ | Targeting glycolysis (glycolysis inhibitors, altering glucose metabolism) | 55 |
| Reduced NADPH | ↑ | Targeting sources of NADPH (methotrexate, metformin, silencing key genes in NADPH-producing pathways) | 66, 67, 72 |
| Other | |||
| Oncogenic mutations | ↑ | 23, 73– 75 | |