Vitamin D analogs in cutaneous malignancies

In this article are reviewed available experimental and clinical studies on vitamin D analogs, and molecular and cellular mechanisms of their antineop lastic activity. In more detail are discussed the antiproliferative and pro -differentiative effects, inhibition of tumor-induced angiogenesis and indu ction of apoptosis. The use of vitamin D analogs is however hampered by the ir toxicity. In various experimental systems it was shown that the activiti es of vitamin D analogs can be enhanced by combined application with retino ids or other biological active compounds, such as cytokines and growth fact ors. Retinoids and vitamin D analogs were found to have synergistic inhibit ory effects on tumor cell proliferation and angiogenic capability, and both agents applied simultaneously are efficacious in small doses. Thus combine d therapy could find application in clinical practice. There are up to now only very limited data on the treatment of cutaneous malignancies with vita min D analogs, and it appears that a combined therapy, preferably with reti noids, could be more beneficial. The new synthetic, more potent and less ca lcemic analogs might find wide application in chemotherapy of premalignant and early malignant cutaneous tumors, and could be especially useful for ch emoprevention in the high-risk groups, eg, xeroderma pigmentosum, organ tra nsplant recipients, arsenical keratoses and others.