New vitamin D analogs as potential therapeutics in melanoma

Abstract

Extensive evidence shows that the active form of vitamin D3 – 1α,25-dihydroxyvitamin D3 – plays an important role in cancer prevention, has tumorostatic activity and may potentially be used in therapy for melanoma. Vitamin D3 and its analogs (secosteroids) exert multiple effects on cancer cells, including inhibition of cell growth and induction of differentiation. Activity of secosteroids depends on multiple cellular factors, including expression of the vitamin D receptor. Despite its endogenous origin, the key drawback for the use of pharmacologically effective doses of 1α,25-dihydroxyvitamin D3 is its hypercalcemic effect leading to profound toxicity. The solution may lie in properties of vitamin D3 analogs with modified side chains, which demonstrate low calcemic activity but conserve the anti-tumor properties. Noncalcemic vitamin D compounds were found to be potent in multiple studies that mandate further clinical testing. Finally, recent studies revealed alternative metabolic pathways for secosteroids and new targets in the cells, which opens up new therapeutic possibilities.

Keywords::

• 1α,25-dihydroxyvitamin D3
• melanoma
• secosteroids
• VDR
• vitamin D
• vitamin D analogs
• vitamin D receptor

Financial & competing interests disclosure

This work was supported by a grant from the Polish Ministry of Science and Higher Education, project no. N405 623238 (to MA Zmijewski), and grant AR052190 from the NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases (to AT Slominski). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.