Pharmacoproteomics

Since disease processes lead to protein changes, it is of paramount importance to consider the relationship between disease and therapy at the protein level (Anderson and Anderson 1998). The objective of modern pharmacoproteomics is the identification of phenotypic differences in drug metabohsm or response and the subsequent examination of candidate proteins for variations that underUe the observed phenotypes. Instead of focusing on a few protein targets, pharmacoproteomics takes a more global approach in order to capture complicated patterns of protein expression (Anderson and Anderson 1998 Petricoin III et al. 2002). 

Witzmann FA, Grant RA. Pharmacoproteomics in drug development. Phar-macogenomics J 2003 3 69-76. 

Acknowledgments This chapter has been realized within the frame of the research project Integrative cellular pharmacokinetics/pharmacodynamics/pharmacoproteomics studies of anticancer TKIs in leukemia (SNF grant no. 310030 138097/1 to LAD) supported by the Swiss National Science Foundation (SNF, Switzerland). It also benefited from the support of the SNF-funded initiative Nano-Tera (ISyPeM project [269] to TB). 

We have discussed both target receptors and pharmacokinetics in this book. Protein manufacture is under direct genetic control, and two factors are of particular relevance here. First, the precise structure and function of protein macromolecules (receptors) targeted by a specific drug molecule will vary in different individuals. Since the structure and function of the protein are directly related to how the drug molecule will interact with that protein, individuals responses to the drug will vary. Second, there are genetic variations in metabolic enzymes (proteins) and hence metabolism. Both of these processes fall neatly into the domain of pharmacoproteomics (see Section 14.8). 

Bioinformatics is of enormous benefit in proteomic and pharmacoproteomic research. Structural bioinformatics and functional bioinformatics are powerful... 

In addition to screening for new therapeutic targets for lead candidate selection, pharmacogeneomics and pharmacoproteomics have a number of other preclinical and clinical applications. 

The expectations of pharmacogenetics and its progeny, pharmacoproteomics (understanding of and drug effects on protein variants), are high. They include ... 

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