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An Orthotopic Murine Model of Human Prostate Cancer Metastasis
Published on: September 18, 2013
The role of vitamin D in prostate cancer
Abstract:
Prostate cancer is the second leading cause of cancer deaths in men in the United States. Developing new treatment strategies is critical to improving the health of men. This article will be a general review of the field with a focus on research from our laboratory. Our research has focused on four areas in which we have pursued the possible use of 1alpha,25(OH)(2)D(3) and its analogs to treat prostate cancer: 1) The ability of 1alpha,25(OH)(2)D(3) to up-regulate androgen receptors in LNCaP human prostate cancer cells. The implications of this finding on 1alpha,25(OH)(2)D(3)'s ability to inhibit cell growth in vivo are unclear at present.2) The reasons for an inability of 1alpha,25(OH)(2)D(3) to inhibit DU 145 prostate cancer cell growth were explored. We found that combination of an imidazole drug, Liarozole, with 1alpha,25(OH)(2)D(3) was capable of inhibiting DU 145 cell growth.3) A number of low-calcemic vitamin D analogs exhibit potent anti-proliferative activity on prostate cancer cells. We have developed a novel approach using the yeast two-hybrid system to screen for potent analogs.4) The results of a clinical trial of 1alpha,25(OH)(2)D(3) treatment of patients with early recurrent prostate cancer. We provide preliminary evidence that 1alpha,25(OH)(2)D(3) may be effective in slowing the rate of PSA rise in selected cases of prostate cancer. In conclusion, we believe that 1alpha,25(OH)(2)D(3) has a role in the treatment and/or prevention strategies being developed for prostate cancer. However, to increase antiproliferative potency without increasing side-effects, the use of less calcemic analogs appears to be the most reasonable approach.
Insights
Vitamin D (1alpha,25(OH)(2)D(3)) and its analogs show promise for treating prostate cancer by inhibiting cell growth and potentially slowing PSA rise. Less calcemic analogs offer a promising strategy to enhance anti-proliferative effects without increasing side effects.
Area of Science:
- Urology
- Oncology
- Endocrinology
Background:
- Prostate cancer is a leading cause of cancer death in men.
- New treatment strategies are urgently needed.
- Vitamin D compounds are being investigated for their anti-cancer properties.
Purpose of the Study:
- To review research on 1alpha,25(OH)(2)D(3) and its analogs for prostate cancer treatment.
- To explore the mechanisms of action and potential therapeutic applications.
- To present findings from laboratory research and a clinical trial.
Main Methods:
- Investigated 1alpha,25(OH)(2)D(3) effects on androgen receptors in LNCaP cells.
- Explored combination therapy with Liarozole for DU 145 cells.
- Utilized yeast two-hybrid system to screen for vitamin D analogs.
- Conducted a clinical trial for early recurrent prostate cancer.
Main Results:
- 1alpha,25(OH)(2)D(3) up-regulated androgen receptors in LNCaP cells.
- Combination therapy inhibited DU 145 cell growth.
- Identified potent, low-calcemic vitamin D analogs.
- Preliminary clinical data suggest 1alpha,25(OH)(2)D(3) may slow PSA rise.
Conclusions:
- 1alpha,25(OH)(2)D(3) holds potential for prostate cancer treatment and prevention.
- Less calcemic analogs offer a promising approach to improve efficacy and reduce side effects.
- Further research and development of vitamin D analogs are warranted.
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