Please use this identifier to cite or link to this item: http://hdl.handle.net/1946/4029
Previous studies have found certain NAT2 alleles to be associated with clinical outcomes of thalidomide based therapies administered to patients with prostate cancer. The purpose of this study was to validate previous associations and to reveal the molecular mechanism behind the association between NAT2 alleles and thalidomide treatment. Analysis of toxicity data, from a trial where patients with prostate cancer received thalidomide, revealed associations with NAT2 alleles, which is in accordance with earlier studies. Attempts to reveal the molecular mechanism behind these associations included testing for direct NAT2 metabolism of thalidomide with an in vitro assay using human NAT2 cytosol. NAT2 expression in the prostate was also tested with both western blotting and immunofluorescence techniques. The results indicate that thalidomide is not directly metabolized by NAT2. Western blotting and immunofluorescence experiments showed that NAT2 is expressed at detectable levels in the prostate, which suggests that there could be a gene-drug interaction between thalidomide and NAT2 in the prostate tumor. It is still unclear why these clinical associations are present. The results suggest that direct NAT2 metabolism of thalidomide can not explain differences in clinical outcomes from thalidomide based therapy; however, it could be that NAT2 interacts with a pathway that opposes thalidomide action in the prostate.
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