1149 Review ISSN 1462-2416 10.2217/PGS.10.97 © 2010 Future Medicine Ltd Pharmacogenomics (2010) 11(8), 1149–1167 PeRsPective Realities and expectations of pharmacogenomics and personalized medicine: impact of translating genetic knowledge into clinical practice Clinicians have known for decades that sub- stantial interindividual variability can occur in the clinical response to drug treatments for acute and chronic diseases. The proportion of patients who respond positively to their medi- cations is, on average, only approximately 50% (ranging from 25 to 60%), implying that the rest of the patient population is not receiving the proper medication or is suffering from sig- ni icant therapeut ic delays by switching from one medication to another until appreciable clinical bene it is attained [1] . Furthermore, the onset of side effects can manifest itself in drastically different patterns within the same therapeutic regime. Adverse drug reac- tions (ADRs) represent a frequent event esti- mated to be between the fourth and sixth leading cause of death in the USA, with fatal ADRs occurring in 0.32% of patients [2] . Data from the UK [201] show that ADRs also have a cumbersome economic burden on national healthcare systems, leading to costs equivalent to GB£380 million a year. ADRs can be unpre- dictable, and broader knowledge of predispos- ing factors would be of great help in increasing prevention capabilities. It has been shown that the great heterogeneity in the phenotypic expression of the drug treat- ment response trait and ADRs is determined by a complex interplay of multiple genetic variants and environmental factors [3,4] . The complex nature of treatment response traits greatly increases the need for the design of personal- ized prescriptions that should take advantage of the creation of a structured informational framework of phenotypic, environmental and genetic data, ultimately leading to the reduc- tion of the very high incidence of ADRs and therapeutic failure [5] . Over the years, research on the genetic pre- dictors of drug response has involved an ever wider array of molecular targets, so that the original deinition evolved from pharmaco- genetics, which assumes investigation of a spe- ci ic or l imited number of candidate genetic markers, to pharmacogenomics, relecting the broader perspective of analyzing molecular determinants at the genome-, transcriptome- and proteome-wide level. Currently, pharmaco- genomics is being adopted as a unique tool for achieving different goals. On one hand, phar- macogenomic approaches are used to identify biomarkers and targets of currently prescribed medications as a source of new molecules suit- able for the drug-development process. On the other hand, pharmacogenomic-based tech- niques are used as diagnostics tools to select and/or dose currently available therapeutics. However, these discoveries do not lead to per- sonalized therapeutics unless predictive tests are proactively codeveloped, together with new drug candidates [6,7] . The implementation of genetic data for a better prediction of response to medications and adverse drug reactions is becoming a reality in some clinical ields. However, to be successful, personalized medicine should take advantage of an informational structured framework of genetic, phenotypic and environmental factors in order to provide the healthcare system with useful tools that can optimize the effectiveness of speciic treatment. The impact of personalized medicine is potentially enormous, but the results that have so far been gathered are often dificult to translate into clinical practice. In this article we have summarized the most relevant applications of pharmacogenomics on diseases to which they have already been applied and ields in which they are currently emerging. The article provides an overview of the opportunities and shortcomings of the implementation of genetic information into personalized medicine and its full adoption in the clinic. In the second instance, it provides readers from different ields of expertise with an accessible interpretation to the barriers and opportunities in the use/adoption of pharmacogenomic testing between the different clinical areas. KEYWORDS: adverse drug reaction n cancer n cardiovascular disease n genetic test n infectious disease n personalized medicine n pharmacogenomics n psychiatry Alessio Squassina 1 , Mirko Manchia 1,2 , Vangelis G Manolopoulos 3 , Mehmet Artac 4 , Chrisina Lappa- Manakou 5 , Sophia Karkabouna 5 , Konstaninos Mitropoulos 5 , Maria Del Zompo 1 & George P Patrinos † 1 University of Cagliari, Cagliari, Italy 2 Dalhousie University, Halifax, Nova Scoia, Canada 3 Democritus University of Thrace School of Medicine, Alexandroupolis, Greece 4 Selcuk University, Konya, Turkey 5 Erasmus University Medical Center, Roterdam, The Netherlands † Author for correspondence: University of Patras, Department of Pharmacy, School of Health Sciences, University Campus, Rion, GR-265 04, Patras, Greece Tel.: +30 261 096 9834 Fax: +30 261 096 9834 gpatrinos@upatras.gr For reprint orders, please contact: reprints@futuremedicine.com