In this article are reviewed available experimental and clinical studies on 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, eg. xeroderma pigmentosum, organ transplant recipients, arsenical keratoses and others.
Keywords: Vitamin D Analogs, Cutaneous Malignancies, Cell Proliferation, receptor VDR, JCA 1 cell line, MCF6, DMBA, Cervical Tumors, Transglutaminase K, Cytokeratin 10, Ki 60, Immortalized keratinocyte HPKIA, Cancer, Immunosuppressive, Angiogenesis, Retinoids, Cytokines
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