Chemopreventive Efficacy of Natural Vitamin D and Synthetic Analogs

Abstract

The activities of vitamin D and synthetic vitamin D analogs (deltanoids) are primarily mediated through binding to vitamin D receptors (VDRs), members of the steroid/thyroid receptor superfamily. Chemopreventive properties of this class of compounds include in vitro and in vivo antiproliferative, pro-apoptotic, pro-differentiating, and anti-angiogenic activities. Natural vitamin D and a number of deltanoids have shown chemopreventive efficacy in preclinical studies. Although also supported by substantial epidemiologic data, the development of natural vitamin D as a cancer chemopreventive has been hindered by dose-limiting hypercalcemic effects. Unfortunately, these same safety concerns also apply to many deltanoids, including those approved for treatment of secondary hyperparathyroidism in patients with end-stage renal disease. However, several new synthetic deltanoids have recently shown promise in preclinical safety and chemopreventive efficacy studies.