Vitamin D and Prostate Cancer

There is substantial interest in whether vitamin D signaling plays a role in reducing risk for prostate cancer and in its use as a therapeutic target in prostate cancer. Vitamin D is synthesized in the skin through a UVB-mediated reaction and subsequently hydroxylated to form 1,25-dihydroxyvitamin D 3 , the ligand for the vitamin D receptor (VDR), a hormone activated transcription factor. Epidemiological studies correlating prostate cancer risk with reduced exposure to sunlight have suggested that vitamin D reduces risk, but the conclusions from studies of vitamin D metabolites have been variable. Similarly, despite promising results in preclinical studies, attempts to target VDR clinically have been less successful. This chapter reviews what is known regarding the actions of VDR in prostate and in prostate cancers and the evidence for activation of VDR as a strategy to reduce risk and/or treat prostate cancer. The chapter summarizes the evidence for a role in reducing prostate cancer risk and discusses the possibility that aberrant vitamin D metabolism contributes to the difficulties in correlating serum vitamin D metabolites with the level of VDR activation in cells. Also discussed are other mechanisms for resistance to the beneficial actions of VDR and strategies to optimize VDR activity. These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.