Page 56 - Vitamin D and Cancer

2 The Molecular Cancer Biology of the VDR 43

The challenge is to model the spatio-temporal actions of the NR network and, in
particular, the extent to which the VDR exerts critical control over transcription and
translation. Such an understanding requires a clear awareness of the chromatin
architecture and context of the promoter regions (e.g., histone modifications, DNA
methylation), genomic organization, gene regulation hierarchies, and 1a,25(OH) D -
2 3
based metabolomic cascades, all within the context of specific cell backgrounds.
The ultimate research goal will be to translate this understanding to strategies that
can predict the capacity of subsets of VDR actions to be regulated and targeted in
distinct cell types and exploited in discrete disease settings.
The current lack of an integral view of how these interactions bring about func-
tion and dysfunction, for example, in the aging human individual, can be attributed
to the limitations of previously available techniques and tools to undertake such
studies. The implementation of post-genomic techniques together with bioinfor-
matics and systems biology methodology is expected to generate an integral view,
thereby revealing and quantifying the mechanisms by which cells, tissues, and
organisms interact with environmental factors such as diet [207, 208].

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