Pharmacogenomics: Current State-of-the-Art

Abstract

The completion of the human genome project 10 years ago was met with great optimism for improving drug therapy through personalized medicine approaches, with the anticipation that an era of genotype-guided patient prescribing was imminent. To some extent this has come to pass and a number of key pharmacogenomics markers of inter-individual drug response, for both safety and efficacy, have been identified and subsequently been adopted in clinical practice as pre-treatment genetic tests. However, the universal application of genetics in treatment guidance is still a long way off. This review will highlight important pharmacogenomic discoveries which have been facilitated by the human genome project and other milestone projects such as the International HapMap and 1000 genomes, and by the continued development of genotyping and sequencing technologies, including rapid point of care pre-treatment genetic testing. However, there are still many challenges to implementation for the many other reported biomarkers which continue to languish within the discovery phase. As technology advances over the next 10 years, and the costs fall, the field will see larger genetic data sets, including affordable whole genome sequences, which will, it is hoped, improve patient outcomes through better diagnostic, prognostic and predictive biomarkers.

Human leukocyte antigen genetic risk factors of drug-induced liver toxicology

“…As genotyping/sequencing technologies advance and costs fall, increasing opportunities for point of care pre-treatment genetic testing are anticipated, leading to improved patient outcomes through the development of diagnostic, prognostic and predictive biomarkers [90]. Advances in next-generation sequencing herald a new era where it is possible to consider variations in an entire genome to detect extremely rare genetic risk factors.…”

The Importance of Patient-Specific Factors for Hepatic Drug Response and Toxicity

“…Notably, this list only partly overlaps with the genetic testing requirements by American, European and Japanese regulatory agencies (Figure 1). Genotype-guided prescribing is only implemented for few drugs in the current clinical routine due to a variety of reasons, including: (i) problems in replicating identified associations, especially in the case of rare events; (ii) heterogeneous genetic nomenclature and non-standardized results reporting; as well as (iii) ethical; and (iv) regulatory considerations (reviewed in [6,7]). Therefore, overcoming these obstacles is of critical importance to further personalize pharmaceutical treatment, which could result in decreased morbidity and mortality for patients and a more efficient distribution of limited health-care resources.…”

Companion diagnostics—a tool to improve pharmacotherapy

“…The main contributor to this variability is diseases heterogeneity, and patients who have similar diagnoses very often respond differently to the same pharmacological intervention, with great variability in both efficacy and safety outcome. Despite having discussed personalized medicine for more than a decade, we still see that most drug prescriptions are largely based on 'trial and error' and not on solid biomarker data (1,4,5). For serious chronic diseases, such an approach can have unfortunate medical consequences for the individual patients.…”