Vitamin D and prostate cancer

Following epidemiological observations that suggested links between low vitamin D exposure and increased risk of prostate cancer, interest in clarifying a potential role of this steroid hormone in prostate cancer has grown. While the results have been mixed, epidemiologic studies have suggested that severe vitamin D deficiency may increase the risk of clinically important prostate cancer. Laboratory investigation provides clear evidence of the potential of vitamin D receptor (VDR) ligands to induce growth arrest and promote apoptosis in a variety of cancer models. Because there are hundreds of vitamin D responsive genes, multiple mechanisms for these observations have been proposed. Prompted by clear evidence of dose-dependent antitumor effects, efforts to harness this knowledge to improve patient outcomes has focused primarily on the development of high dose calcitriol, often in combination with other anti-neoplastic agents. After encouraging phase II results, the phase III effort failed when excess deaths were reported in the experimental arm of a trial that compared calcitriol with docetaxel to prednisone with docetaxel. In addition to targeting the vitamin D receptor, the two arms of this study differed with respect to the dose, schedule, and dose intensity of the chemotherapy agent and steroids, making definitive conclusions about the potential of vitamin D receptor targeted therapy difficult. No prospective randomized studies aimed at prostate cancer prevention have been reported. Continued efforts to target vitamin D signaling for prostate cancer prevention and treatment are needed in light of the strong preclinical evidence supporting the importance of this signaling pathway. Better understanding of the human prostate cancer's biologic heterogeneity in vitamin D sensitivity may allow for more robust identification of ways in which vitamin D can be harnessed to help men who suffer from this disease.