Current progress in using vitamin D and its analogs for cancer prevention and treatment

Vitamin D has long been known for its physiological role in mineral homeostasis through its actions on the intestines, kidneys, parathyroid glands and bone. However, recent observations of antiproliferative, prodifferentiating and antiangiogenic effects elicited by the bioactive form of vitamin D (1,25[OH](2)D(3)) in a broad range of cancers is less well understood. Here, we review the increasing epidemiological and experimental evidence that supports the development of 1,25(OH)(2)D(3) and vitamin D analogs as preventative and therapeutic anticancer agents. Furthermore, this review summarizes the preclinical and clinical studies of vitamin D and its analogs over the past decade, indicating the current problems of dose-limiting toxicity from hypercalcemia and large interpatient variability in pharmacokinetics. A better understanding of how genetic variants influence vitamin D status should not only improve cancer risk predictions, but also promote the development of vitamin D analogs with more specific actions to improve therapeutic outcomes.