Improve efficacy of topical ALA-PDT by calcipotriol through up-regulation of coproporphyrinogen oxidase

Fluorouracil Enhances Photodynamic Therapy of Squamous Cell Carcinoma via a p53-Independent Mechanism that Increases Protoporphyrin IX levels and Tumor Cell Death

“…Eight enzymes are required for heme synthesis (summarized in (25)) and six of these (ALAS, ALAD, PBGS, PBGD, CPO and FC) have been studied in the literature in the context of ALA-PDT to assess their importance during ALA-PDT in different experimental contexts and cell types (17). In previous work on MTX or calcitriol as neoadjuvants, MTX preconditioning affected primarily CPO (18), whereas both CPO and FC were strongly affected after calcitriol (19, 26). In the current study, 5-FU led to increased CPO and decreased FC expression.…”

“…1C, 1D); this approach revealed a 3.5-fold PpIX enhancement due to 5-FU. In previous studies using MTX or calcitriol, a 3–4 fold increase in PpIX levels resulted in up to 5-fold increase in cell death in cells or tumors receiving cPDT (18, 19, 26). …”

A randomized split-scalp study comparing calcipotriol-assisted methyl aminolaevulinate photodynamic therapy (MAL-PDT) with conventional MAL-PDT for the treatment of actinic keratosis

“…Although they are not completely understood, the mechanisms for calcipotriol‐enhanced PpIX production are partly increased uptake of the photosensitizer in differentiated cells and partly increased expression of the porphyrin synthesis enzyme coproporphyrinogen oxidase and decreased ferrochelatase . Another possible mechanism of action of topical calcipotriol is the induction of antitumour immune response .…”

Vitamin D and Vitamin D Analogs as Adjuncts to Field Therapy Treatments for Actinic Keratoses: Current Research and Future Approaches

“…(2) Higher rates of recurrence at 12 months seen in the FU and cryotherapy-treated group (3) Imiquimod was judged to have the best cosmetic outcomes 5% 5-FU vs. imiquimod [78] (1) 5-FU was more effective than imiquimod in exposing subclinical AK, reducing AK counts at 24 weeks (94% vs. 66%), achieving complete clearance at 24 weeks (84% vs. 24%) (2) Erythema as a side effect was higher in the 5-FU arm 0.5% 5-FU vs. placebo [79] (1) Mean AK count reduction at 4 weeks was 62.4% in the 5-FU group vs. 28.8% in the vehicle group (2) Complete clearance was 16.7% with FU and 0% in the vehicle group 0.5% 5-FU vs. ALA PDT (blue light) vs. ALA PDT (laser light) [80] (1) 5-FU was as equivalent to blue-PDT in achieving >75% AK clearance (2) Cumulative clearance rate at 4 weeks after treatment for 5-FU, blue-PDT, and PDL-PDT was 79%, 80%, and 50%, respectively (3) PDT using ALA plus laser light was the least effective among the treatment arms (4) Both PDT treatment arms had lower side effect profile than 5-FU Long-term efficacy of 5% 5-FU [81] (1) At 6 months after treatment, fewer AK were found in 5-FU treated patients compared to control (no treatment) (2) Higher complete AK clearance in 5-FU vs. control (38% vs. 17% at 6 months) (3) Fewer spot treatments at 6-month intervals and in between study visits were reported in the 5-FU treated patients (4) No difference in the number of hypertrophic AK between the two groups 5% 5-FU prevention of skin cancer [63] (1) At 1 year after treatment, a 75% risk reduction of developing squamous cell carcinoma was seen in patients treated with 5-FU vs. vehicle cream (2) No significant effect was seen in the development of basal cell carcinoma 6 Journal of Skin Cancer tolerated PDT with vitamin D analogs well [119]. Mechanistic studies suggest that the addition of calcipotriol increases coproporphyrinogen oxidase, a heme breakdown enzyme, which creates additional ROS within cancerous cells, increasing apoptosis in these cells [120].…”