SEIBUTSU BUTSURI KAGAKU

Drug responses and adverse side effects widely vary among individuals. Researchers have focused on genetic polymorphisms that encode drug-metabolizing enzymes, drug transporters, and drug receptors, as the chief causes of the variations in drug responses. Personalized drug therapy involves analysis of genetic polymorphisms associated with drug responses before drug administration and selection of drugs and doses according to the individual genetic background. Establishment of personalized drug therapy is expected to contribute to medical economy through avoidance of wasteful drug administration. Regarding the many genes involved in drug responses, to date, the application of patient genetic information to personalized drug therapy has been achieved at the practical level. Information on pharmacogenomics will be critical in medical practice in the near future. In this review, we summarize the recent information on genetic polymorphisms involved in drug metabolism, responses, and adverse drug reaction.

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Proteomics is the systematic study of a proteome, the complete set of proteins found in a given cell type or in body fluids. Although technological advances have made proteomics useful for discovery of markers in various fields of medicine, it is not an easy task to bring the biomarker candidates from bench to bedside.
By comprehensive serum proteome analyses, we previously identified a 5.9 kDa peptide fragment of fibrinogen α C-chain (FIC 5.9) as a novel biomarker candidate for heavy drinking. More recently, using a sandwich ELISA to specifically detect this peptide, FIC 5.9 was found to be a sensitive marker to detect hepatic fibrosis at an early stage.
Mortality due to hepatocellular carcinoma (HCC) is still high because of the late diagnosis of HCC. There is a need for sensitive serum markers for HCC to improve its early detection. We previously performed comparative proteome analyses of surgically resected HCC tissues and their adjacent non-tumor tissues using two-dimensional fluorescence difference gel electrophoresis, and identified a number of proteins overexpressed in HCC tissues. We then tested diagnostic values of autoantibodies to these overexpressed proteins and found that serum anti-Ku86 shows high sensitivity for the early detection of HCC in patients with HCV-related liver cirrhosis.
Collaborative works of basic scientists, clinicians and diagnostic industries are necessary to discover novel biomarkers and bring them to clinical fields, which eventually will lead to effective patient cares.

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