Vitamin D and intervention trials in prostate cancer: from theory to therapy

Studies of vitamin D and prostate cancer have advanced rapidly from the hypothesis that vitamin D deficiency increases the risk of prostate cancer to intervention trials of vitamin D administration in clinical cancer. The hormonal form of vitamin D, 1,25(OH)(2)D, exerts prodifferentiating, antiproliferative, anti-invasive, and antimetastatic effects on prostate cells. Moreover, normal prostate cells synthesize 1,25(OH)(2)D from serum levels of the prohormone, 25-hydroxyvitamin D. The autocrine synthesis of 1,25(OH)(2)D by prostatic cells provides a biochemical mechanism whereby vitamin D may prevent prostate cancer. Many prostate cancer cells have lost the ability to synthesize 1,25(OH)(2)D but still possess 1,25(OH)(2)D receptors. This suggests that whereas vitamin D (e.g., cholecalciferol) might prevent prostate cancer, existing prostate tumors likely would require treatment with 1,25(OH)(2)D and/or its analogs. The major obstacle to the use of 1,25(OH)(2)D in patients therapeutically is the risk of hypercalcemia. Several maneuvers to reduce this risk, including pulse dosing and the use of less calcemic 1,25(OH)(2)D analogs, have been explored in Phase I-III clinical trials. Once merely a promise, vitamin D-based therapies for prostate cancer may soon be medical practice.