Vitamin D in the prevention and treatment of pancreatic cancer

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Pancreatic cancer is one of the most lethal cancers with a 5-year survival rate of less than 5 %. The more aggressive nature of this disease contributes to its usual late stage diagnosis that makes most patients unsuitable for receiving curative surgery. In addition, traditional chemotherapy and radiotherapy are not effective in this group of patients, leaving little therapeutic choices for them. 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3), the biologically active form of vitamin D3, is now recognized to regulate more than 200 genes and to exert a variety of biological effects in almost every tissue in the body, including antiproliferative, pro-apoptotic, pro-differentiation and anti-angiogensis effects in cancer cells in vivo and in vitro. The clinical use of 1α,25(OH)2D3 is impeded by the lethal side effects of hypercalcemia and hypercalciuria. Therefore, 1α,25(OH)2D3 analogs, which are either equipotent or more potent than 1α,25(OH)2D3 in inhibiting tumor cell growth but with less hypercalcemic and hypercalciuric side effects, have been developed for the treatment of different cancers, and either used alone or in combination with other anticancer agents. The inversed association between vitamin D status and incidence of many forms of cancer has suggested that vitamin D could play a role in the prevention of these types of cancer. Although it is still controversial whether this association exists for pancreatic cancer, biochemical evidence clearly indicates that pancreatic cancer cells are responsive to the inhibitory effect of 1α,25(OH)2D3 and its analogs in vitro and in vivo. In this chapter, we summarize the recent progress in the epidemiological studies of sunlight, and vitamin D nutritional status, and discuss the biochemical studies using 1α,25(OH)2D3 and its analogs in pancreatic cancer cells with particular emphasis on the molecular mechanism of anti-cancer actions of 1α,25(OH)2D3.