Vitamin D for the prevention and treatment of pancreatic cancer

Pancreatic cancer is ranked fi fth among cancer-related deaths worldwide with a 5-year survival rate of less than 5%. Currently, surgery is the only effective therapy. However, most patients are diagnosed in the late stage and are not suitable for receiving curative surgery. Moreover, pancreatic cancer doesn’t respond well to traditional chemotherapy and radiotherapy, leaving little effective treatment for advanced pancreatic cancer cases. 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3], the biologically active form of vitamin D3, was originally identifi ed during studies of calcium and bone metabolism, though it is now recognized that it exerts biological effects in almost every tissue in the body. Abundant evidence has shown that 1α,25(OH)2D3 has antiproliferative, apoptotic, pro-differentiation and antiangiogensis effects in many types of cancer cells in vivo and in vitro, including breast, prostate, and colon. Similarly, the antitumor growth effect of 1α,25(OH)2D3 on pancreatic cells has been demonstrated. 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 fewer hypercalcemic and hypercalciuric side effects, have been developed for the treatment of different cancers. Recently, a pre-clinical study demonstrated that a less calcemic analog of 1α,25(OH)2D3, 19-nor-1α,25(OH)2D2 (Paricalcitol), is effective in inhibiting tumor growth in vitro and in vivo , via upregulation of p21 and p27 tumor suppressor genes. Studies on the anti-tumor effects of a more potent analog of Paricalcitol are underway.1α,25(OH)2D3 and its analogs are potentially attractive novel therapies for pancreatic cancer.