Melanoma represents a significant clinical problem affecting a large segment of the population with a relatively high incidence and mortality rate. Ultraviolet radiation (UVR) is an important etiological factor in malignant transformation of melanocytes and
melanoma development. UVB, while being a full
carcinogen in melanomagenesis, is also necessary for the cutaneous production of
vitamin D3 (D3).
Calcitriol (
1,25(OH)2D3) and novel CYP11A1-derived hydroxyderivatives of D3 show anti-
melanoma activities and protective properties against damage induced by UVB. The former activities include inhibitory effects on proliferation, plating efficiency and anchorage-independent growth of cultured human and rodent
melanomas in vitro, as well as the in vivo inhibition of
tumor growth by
20(OH)D3 after injection of human
melanoma cells into immunodeficient mice. The literature indicates that low levels of 25(
OH)D3 are associated with more advanced
melanomas and reduced patient survivals, while single nucleotide polymorphisms of the
vitamin D receptor or the D3
binding protein gene affect development or progression of
melanoma, or disease outcome. An inverse correlation of VDR and
CYP27B1 expression with
melanoma progression has been found, with low or undetectable levels of these
proteins being associated with poor disease outcomes. Unexpectedly, increased expression of
CYP24A1 was associated with better
melanoma prognosis. In addition, decreased expression of
retinoic acid orphan receptors α and γ, which can also bind
vitamin D3 hydroxyderivatives, showed positive association with
melanoma progression and shorter disease-free and overall survival. Thus, inadequate levels of biologically active forms of D3 and disturbances in expression of the target receptors, or D3 activating or inactivating
enzymes, can affect melanomagenesis and
disease progression. We therefore propose that inclusion of
vitamin D into
melanoma management should be beneficial for patients, at least as an adjuvant approach. The presence of multiple hydroxyderivatives of D3 in skin that show anti-
melanoma activity in experimental models and which may act on alternative receptors, will be a future consideration when planning which forms of
vitamin D to use for
melanoma therapy.