Conclusions And Future Prospects

Despite the pessimism, interest in pharmacogenetics is unlikely to vanish in the future. However, before being stably integrated into the clinical practice, pharmacogenetics needs to be shown to significantly improve the outcome of drug treatment in order to outweigh the extra costs associated with the widespread application of genetic techniques to patient management. The identification of genes implicated in the response to anticancer agents has created the scientific basis for novel approaches, for example, using proteomics, to evaluate the role of gene products in the response of cells to drugs (107). The rationale behind this approach may be summarized as follows: (i) several mutations are silent and do not interfere with the function of gene products, (ii) the SNPs affecting a gene may be so numerous and their different combinations (haplotypes) so complex that the evaluation of protein function turns out to be simple and more informative, (iii) some genes are characterized by posttranscriptional regulation, such as TS (108), therefore gene expression may not be directly related to the synthesis of the protein product, and (iv) many additional factors may contribute to the function of proteins, making it difficult to predict the final effect of all factors considered as a whole.

The time delay between drug introduction into clinical practice and the search for genetic factors affecting outcome and tolerability may be significantly reduced by the introduction of pharmacogenetics and pharmacogenomics in clinical studies, and it should be of value in identifying patients at risk of major toxicity or therapeutic failure.

In conclusion, advances in molecular techniques have led to the discovery of genetic factors related to drug sensitivity or resistance within cancer cells, including those in metabolic pathways and cellular targets. The ultimate aim of pharmacogenetics will thus be the segmentation of patients into discrete categories according to their likelihood of response to drugs and the identification, on an individual basis, of subjects with "rare" unfavorable genotypes at risk of major toxicities following treatment administration.

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