Vitamin D: Cancer and differentiation

This chapter provides an overview of the history and the current state of knowledge regarding the role of vitamin D in tumor cell growth regulation, treatment of cancer and development of potent synthetic vitamin D analogs. It addresses the recent developments in studies of vitamin D and cancer, regulation of tumor cells, possible mechanisms, and clinical applications. Based on this understanding, it indicates that the data obtained so far, on the distribution of the VDR in a broad range of tumors and the inhibition of cancer cell growth, angiogenesis, metastasis, inflammation, and PTHrP synthesis as well as the stimulation of differentiation and apoptosis by 1,25(OH)₂D₃, all hold promise for the development of treatment strategies based on vitamin D₃ use in a wide range of cancers. Combination of vitamin D₃ with other antitumor drugs, hormones, or growth factors is an important additional therapeutic option. The clinical application is enhanced by the development of 1,25(OH)₂D₃ analogs with potent growth-inhibitory actions and reduced hypercalcemic activity. Nevertheless it is crucial for the coming years to deliver strong clinical trials to support the potential of vitamin D in cancer treatment uncovered by investigation of cultured cells, animal models, and epidemiological studies.