In this article are reviewed available experimental and clinical studies and
vitamin D analogs, and molecular and cellular mechanisms of their
antineoplastic activity. In more detail are discussed the antiproliferative and pro-differentiative effects, inhibition of
tumor-induced angiogenesis and induction of apoptosis. The use of
vitamin D analogs is however hampered by their toxicity. In various experimental systems it was shown that the activities of
vitamin D analogs can be enhanced by combined application with
retinoids or other
biological active compounds such as
cytokines and
growth factors.
Retinoids and
vitamin D analogs were found to have synergistic inhibitory effects on
tumor cell proliferation and angiogenic capability, and both agents applied simultaneously are efficacious in small doses. Thus combined
therapy could find application in clinical practice. There are up to now only very limited data on the treatment of cutaneous
malignancies with
vitamin D analogs and it appears that a combined
therapy, preferably with
retinoids, could be more beneficial. The new synthetic, more potent and less calcemic analogs might find wide application in
chemotherapy of premalignant and early malignant cutaneous
tumors and could be especially useful for
chemoprevention in the high-risk groups, e.g.,
xeroderma pigmentosum, organ transplant recipients, arsenical
keratoses and others.