Will analogs of 1,25-dihydroxyvitamin D(3) (calcitriol) open a new era in cancer therapy?

Published on Wednesday, 29 November 2017


Numerous in vitro and in vivo observations, demonstrating that 1,25-dihydroxyvitamin D(3) is a potent inhibitor of tumor cell growth, provided the rationale for using this seco-steroid hormone to treat patients with leukemia and various types of cancer. However, the therapeutic efficacy of systemically applied vitamin D analogs for treating cancer has not yet fulfilled its promise. A main reason for these disappointing results is that the use of systemically applied vitamin D analogs is limited by severe side effects, mostly hypercalcemia, at the supraphysiological doses needed to reach clinical improvement.

New concepts for the development of cancer treatment strategies that are based on the use of vitamin D(3) compounds are discussed in this manuscript.

At the moment, different strategies that may enable the application of vitamin D analogs for the treatment of various malignancies, including malignant skin tumors, are employed.

It has been shown that certain vitamin D analogs differ in their intracellular metabolism, nongenomic actions, pharmacokinetics, interaction with the vitamin D binding protein (DBP) or the vitamin D receptor (VDR).

Several of these new concepts are based on recent laboratory results demonstrating that VDR requires heterodimerisation with additional nuclear cofactors such as the retinoid-X receptor (RXR) for sufficient DNA-binding or are based on new findings in the metabolism of vitamin D.

Taken together, these new strategies hold promise that analogs of 1,25-dihydroxyvitamin D(3) may herald a new era in the treatment of various malignancies, including skin cancer.



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See also:

- Vitamin D (analogues and/or derivatives) and cancer;

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- Observations on the Report of a case of pulmonary adenocarcinoma with lymph node, hepatic and osseus metastasis;

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- Evaluation of the safety and efficacy of the first-line treatment with somatostatin combined with melatonin, retinoids, vitamin D3, and low doses of cyclophosphamide in 20 cases of breast cancer: a preliminary report;

- The Di Bella Method (DBM) improved survival, objective response and performance status in a retrospective observational clinical study on 122 cases of breast cancer;

- Complete objective response to biological therapy of plurifocal breast carcinoma.