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Molecular Cancer Therapeutics
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Review

Promise of vitamin D analogues in the treatment of hyperproliferative conditions

Sonoko Masuda and Glenville Jones
Sonoko Masuda
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Glenville Jones
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DOI: 10.1158/1535-7163.MCT-05-0539 Published April 2006
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Abstract

1α,25-Dihydroxyvitamin D3 [1α,25-(OH)2D3; calcitriol] is best known as a hormone involved in calcium homeostasis but is also a potent antiproliferative agent in many cell types, particularly epithelial cells. 1α,25(OH)2D3 mediates its actions through a classic steroid hormone-like transcriptional mechanism by influencing the expression of hundreds of genes. Effects of 1α,25(OH)2D3 have been observed on expression of cell cycle regulators, growth factors and their receptors, apoptotic machinery, metastatic potential, and angiogenesis; all of which have some effect on hyperproliferative conditions. This minireview focuses on the anticancer potential of 1α,25(OH)2D3 and its analogues by summarizing the promising data from animal and human trials of 1α,25(OH)2D3 and some of the more interesting synthetic vitamin D analogues in the treatment of a variety of different animal cancer models and in human patients with advanced cancer. Optimal administration of vitamin D analogues is only just being achieved with high-dose intermittent administration overcoming bioavailability and hypercalcemia problems and combination therapy with cytotoxic agents (taxols and cisplatins), antiresorptive agents (bisphosphonates), or cytochrome P450 inhibitors being attempted. Although the potential of vitamin D as an antiproliferative drug has been realized in the treatment of psoriasis and in parathyroid cell hyperplasia associated with secondary hyperparathyroidism, the search for an anticancer treatment incorporating a vitamin D analogue remains elusive. [Mol Cancer Ther 2006;5(4):797–808]

Keywords:
  • vitamin D
  • calcitriol
  • 1α,25-dihydroxyvitamin D3
  • vitamin D receptor
  • cancer

Footnotes

  • Grant support: Canadian Institutes of Health Research (MT-9475, MMA-38116 and MMA-69106).

    • Accepted February 16, 2006.
    • Received December 27, 2005.
    • Revision received January 31, 2006.
  • American Association for Cancer Research
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Molecular Cancer Therapeutics: 5 (4)
April 2006
Volume 5, Issue 4
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Promise of vitamin D analogues in the treatment of hyperproliferative conditions
Sonoko Masuda and Glenville Jones
Mol Cancer Ther April 1 2006 (5) (4) 797-808; DOI: 10.1158/1535-7163.MCT-05-0539

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Promise of vitamin D analogues in the treatment of hyperproliferative conditions
Sonoko Masuda and Glenville Jones
Mol Cancer Ther April 1 2006 (5) (4) 797-808; DOI: 10.1158/1535-7163.MCT-05-0539
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    • Biochemistry of Vitamin D
    • Rationale for Using Vitamin D Analogues in Cancer Therapy
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Molecular Cancer Therapeutics
eISSN: 1538-8514
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