Clinical translation of genotyping and haplotyping data: implementation of in vivo pharmacology experience leading drug prescription to pharmacotyping

Abstract

The completion of the Human Genome Project has raised expectations for the translation of genomic knowledge into clinical forms that would lead to improved diagnosis of diseases and identification of new drug targets. Such an opportunity is quite challenging within science and society, although there is still uncertainty regarding its outcomes in new drug development and healthcare. Undoubtedly, however, the recent approval by the US FDA of the first two pharmacogenomic tests for genotyping drug-metabolising enzymes is expected to empower and eventually lead to general applicability of various genetic diagnostic tools to improve pharmacotherapy outcomes in the post-genomic era. To this end, the application of genomic knowledge and technologies in everyday clinical practice leads personalised medicine concepts towards the achievement of individualised drug selection and dosage profiling (i.e. pharmacotyping) for ensuring maximum drug effectiveness and safety. Within this framework, pharmacogenomic information can implement the existing clinical pharmacology experience in clinical diagnosis and drug delivery. The latter can be further advanced through the development of workflow information-based operating systems in healthcare to support the utilisation, assessment and outcome of engaged clinical and genomic information. Such a direction may help to suitably revise and adjust clinical regulatory guidelines as well as clinical pharmacology guidelines. This will further facilitate better designing of clinical trials for new drug development as well as pharmacovigilance registries and evaluation of these data. To critically describe the existing environment, this article comprehensively discusses scientific efforts aimed at making clinical translation of genotyping and haplotyping data more efficient and productive in forms that are readily applicable in everyday healthcare. In addition, specific and systematic pharmacogenomic and clinical attempts related to the development of new molecularly targeted drugs, as well as improvement of the efficacy and safety of commonly prescribed drugs, are presented. To this end, the clinical pharmacogenomic experience gained thus far in the use of tyrosine kinase inhibitors in oncology, as well as the process of empowerment through the use of genomic knowledge of the cardiac safety of drugs modulating the function of the human ether-à-go-go-related gene (HERG) potassium channel, represent examples of how the implementation of clinical experience with genomic information guides the development of new drugs and the improvement of pharmacotherapy outcomes.