There is accumulating evidence that the vitamin D3/VDR axis is important in multiple cancers. Epidemiological studies on the association of the occurrence and outcome of cancers with serum 1a,25-(OH)2D3 levels or vitamin D3 status are consistent with vitamin D insufficiency being a factor in the development of certain malignancies, primarily prostate, breast, and colon cancer. Given the direct link between 1a,25-(OH)2D3 and its nutritional precursor vitamin D3, new frontiers in current research include investigating the physiological role of extrarenal 1-hydroxylases in cells prone to cancer. There is also current emphasis on manipulating 1a,25-(OH)2D3 levels in patients with cancer as an alternative means of exploiting the anticancer properties of 1a,25-(OH)2D3. Clinical trials95-97 are under way examining the safety and efficacy of weekly high dose of 1a,25-(OH)2D3 in the presence or absence of docetaxel, carboplatin, or dexamethasone in patients with androgen-independent prostate cancer. These studies follow very encouraging phase II trials in the same settings. These trials demonstrated that high intermittent doses of 1a,25-(OH)2D3 can be administered to patients without toxicity and that 1a,25-(OH)2D3has potential as an anticancer agent.
It is important to identify the appropriate recommended dietary allowance for vitamin D3 to achieve normal health or to overcome the occurrence of above-mentioned vitamin D3 insufficiencies in cancer-prone populations. It is advisable to assure adequate vitamin D3 status in relation to carcinomas of the breast, prostate, and colon, especially if sun exposure is curtailed and/or for individuals having a skin type with increased pigmentation. Because 1a,25-(OH)2D3 and its analogs have the added potential to be used to suppress multiple phases of tumor development such as initiation of carcinogenesis, promotion, and progression, there is definitely a critical need to develop deltanoids as anticancer agents. More experimental approaches are necessary to elucidate the underlying molecular and cellular basis of the anticancer properties of vitamin D3 and its analogs.
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