- Vitamin D analogs
- cancer prevention
- therapy
The Third International Symposium entitled Vitamin D Analogs in Cancer Prevention and Therapy that was organized by the Klinik für Dermatologie, Venerologie und Allergologie, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany, and the Klinik für Frauenheilkunde und Geburtshilfe, Helios Klinikum Krefeld, Krefeld, Germany, was held from May 17-18, 2008 at the hotel “Krefelder Hof” in Krefeld, Germany. Our knowledge about the importance of vitamin D for the prevention of various types of cancer has greatly increased in recent years and new promising concepts for the therapeutic use of vitamin D analogs in oncology are emerging. It was the aim of this scientific meeting to present and to discuss latest developments in epidemiology, molecular oncology, metabolism, biological effects and clinical applications of vitamin D analogs that have led to fascinating new perspectives for the application of these compounds in cancer prevention and therapy. Thirty-five keynote lectures of leading scientists were presented and the resulting conclusions were summarized at the end of this symposium in a round table discussion. Selected articles related to presentations at this symposium are published in this Special Issue of Anticancer Research.
The most important findings and conclusions of this meeting can be summarized as follows: Cancer Prevention: Convincing evidence from epidemiological and laboratory investigations and from animal studies now shows that vitamin D deficiency and insufficiency are largely underrecognized worldwide problems that are associated with a broad variety of severe health problems including higher cancer prevalence and unfavourable courses of cancer. However, there is still an urgent need for additional well-designed studies to define the optimal vitamin D status (25-hydroxyvitamin D serum level) and for campaigns to better inform both the public and the medical profession about health risks related to vitamin D deficiency. An increasing number of epidemiological and laboratory investigations demonstrate an association of various types of cancer including colon, prostate and breast cancer with (i) estimated exposure to solar UV-radiation, (ii) vitamin D intake, or (iii) vitamin D deficiency. Although several of these studies are hampered by methodological problems, including a relatively low number of observation years or difficulties in assessing correct estimates of vitamin D status (exposure to solar UV-radiation, vitamin D intake or 25(OH)D measurements), a large number of epidemiological and laboratory investigations now clearly indicate a connection between vitamin D deficiency and multiple independent diseases including various types of cancer. It has now been recognized that the recent discovery of extrarenal 25(OH)D-1α-hydroxylase activity in a broad variety of different tissues is of particular importance for the role of vitamin D in cancer prevention. There was general consensus at this meeting that further evidence has to be obtained from well-designed studies that are currently being carried out (randomised trials, prospective case-control and cohort studies) using multivariate analysis of a large population and many observation years to clarify the role of vitamin D analogs in cancer prevention and to determine a causal relationship between lack of adequate vitamin D and cancer. In this context, it is of particular importance for future investigations to measure plasma 25(OH)D levels from individuals and not to generally speculate what their vitamin D levels might be using geographical latitude as a parameter of possible exposure to solar UV-radiation.
In vitro investigations: Many presentations were related to antitumor effects of 1,25-dihydroxyvitamin D (1,25(OH)2D, calcitriol) and its analogs. New and relevant laboratory investigations analyzing the molecular mechanisms that underly genomic and nongenomic vitamin D signalling pathways and their importance for antitumor effects of vitamin D analogs were discussed. It was shown that a multitude of independent molecular events is involved in antitumor effects of vitamin D, including effects on cell proliferation, differentiation, apoptosis and DNA repair. The molecular mechanisms for these actions are complex and an understanding of the very early events, in particular, is still missing. Several papers presented at this meeting focused on vitamin D receptor (VDR)-mediated genomic effects, in particular on the impact of chromatin organization of vitamin D target genes, on the recruitment of cofactor proteins to the VDR, the interaction of VDR with components of the basal transcription apparatus, and on the regulation of VDR expression by other molecules.
Cancer Therapy: Our knowledge about the antitumor effects of vitamin D analogs has greatly increased during recent years and results from first clinical trials now indicate that vitamin D analogs may represent promising compounds for cancer therapy, most likely in combination with other agents. However, the era of vitamin D analogs in cancer therapy has just begun and efforts to perform well-designed clinical studies and to develop new vitamin D analogs that reveal less systemic side-effects have to continue. Several presentations were related to safety and efficacy of vitamin D analogs in the treatment of various malignancies. These clinical studies demonstrated that vitamin D analogs represent promising compounds for cancer therapy, at least for palliative treatment in combination with cisplatin, docetaxel or other synergistically acting compounds.
- Copyright© 2009 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved