Vitamin D and pancreatic cancer

• The vitamin D system is altered in pancreatic cancer.
• We examine the clinical and epidemiological evidence on the relation between vitamin D levels and pancreatic cancer.
• We review the experimental and clinical evidence for the action of calcitriol analogues in pancreatic cancer.
• Calcitriol analogues exert their anti-cancer effect by their action on cyclin-dependent kinases p21 and p27.
• Use of calcitriol analogues in pancreatic cancer warrants further clinical trials.

Pancreatic cancer is currently the fourth leading cause of cancer-related death, and it is projected that within the next two decades it will become the second most common cause of death due to cancer. Few patients are diagnosed when surgical resection is feasible and the efficacy of existing chemotherapeutic agents for advanced/metastatic cancer is limited. Thus, there is a need to identify agents that can prevent pancreatic cancer or improve survival in those affected. Vitamin D and its analogues, with their ability to regulate cell growth, differentiation, apoptosis and angiogenesis, may be promising agents. This review explores the published literature about the potential role of vitamin D and its analogues in preventing or treating pancreatic cancer. The vitamin D system is altered in pancreatic cancer. Pancreatic cancer tissue expresses vitamin D receptors, but the calcitriol analogues may affect pancreatic cancer tissue by mechanisms that do not involve interaction with its receptors. Experimental evidence postulates multiple potential mechanisms by which calcitriol analogues may exert their anti-cancer effect, the most common being by action on cyclin-dependent kinases p21 and p27. Use of calcitriol analogues in pancreatic cancer remains largely underexplored and warrants further clinical trials.