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Substantial data indicate the broad importance of vitamin D-based signaling in normal human physiology and the broad effects of vitamin D deficiency. Vitamin D may play a role not only in the control of bone and mineral metabolism, but also appears to be involved in immune function, cardiovascular health, thrombosis and vasculogenesis and neuromuscular function. Considerable epidemiologic data demonstrate that low vitamin D serum levels occur very commonly in normal adult populations and that vitamin D deficiency is associated with an enhanced risk of cancer death from lung, prostate, head & neck, colorectal and other gastrointestinal cancers. In addition, preclinical data provide evidence that calcitriol and other active analogues of calcitriol have anti-proliferative, pro-differentiative, pro-apoptotic and anti-angiogenic activity in numerous in-vitro and in-vivo models. It is quite clear that, while it requires high exposure to calcitriol to induce these effects, such exposure can be readily achieved when high dose intermittent therapy is given.

The following chapters provide excellent and comprehensive discussions of the potential role of vitamin D based therapies in breast, colorectal, prostate cancer and leukemia and myelodysplastic syndromes. These chapters also point out that the focus on these diseases is largely determined by the interests and expertise of the outstanding scientists who have chosen to pursue vitamin D based cancer therapeutics. To our knowledge, every tumor type ever evaluated has shown some biochemical and antiproliferative response to vitamin D. Similarly, vitamin D analogues, especially calcitriol, potentiate almost every cytotoxic agent with which combination therapies have been tested.