CYP2R1 and melanoma: We also observed an increase in VDR mRNA level as well as CYP3A4 and CYP2R1 in A375 cells, the enzymes responsible for 25-hydroxylation of vitamin D en route to its final activation, in melanoma cells treated with cediranib at 1,000 nM concentration, which were 1,25(OH)2D3 pretreated, underlining an intensified vitamin D activation in these conditions (p < 0.05, Figure 9).