Inter-individual variation in drug response is a major hurdle to successful disease management. Some patients will respond well to the introduction of a new medication, others will achieve little or no benefit, some will get worse, many will not tolerate the new drug and an unfortunate few may experience a severe adverse reaction. This uncertainty about the outcome of treatment is a reflection of the empiricism which remains in modern medicine and which has significant social and economic consequences. The concept of personalized medicine is one in which biological information about an individual is used to optimise the diagnosis and management of their disease. It holds promise for the rational use of therapy and the avoidance of poor and potentially life-threatening outcomes. After many years of wishful predictions, we now stand on the cusp of an era of personalized medicine, with applications already emerging in several areas of clinical care and others expected to bear fruit in due course. This is in part due to the success of the Human Genome Project, an improved understanding of human biology, and the widening availability of technologies to support systems biology research. This special issue of Pharmaceuticals will highlight ongoing investigations and recent developments in the pursuit of personalized medicine in several key therapeutic arenas, with particular emphasis on genetic contributors to variation in drug responsiveness.
Graeme J. Sills, Ph. D.
Increasing evidence for the role of pharmacogenetics in treatment resistance to the antiplatelet agent clopidogrel has been gained during the last years. Apart from CYP2C19 genetic polymorphisms, nongenetic factors, particularly drug-drug interactions, age and other clinical characteristics influence the interindividual variability in clopidogrel [...] Read more.
Drug-induced hypersensitivity reactions are of major concern and present a burden for national healthcare systems due to their often severe nature, high rate of hospital admissions and high mortality. They manifest with a wide range of symptoms and signs, and can be initiated [...] Read more.
Hypertension is a major public health problem, but measures to reduce blood pressure and thus cardiovascular risk are complicated by the high prevalence of treatment resistance, despite the availability of multiple drugs. Drug side-effects contribute considerably to suboptimal blood pressure control. Clinicians must [...] Read more.
Prescribers have been practicing stratified medicine for many years. Patient characteristics, usually non-genetic, including age, comorbidities and concomitant medications are taken into account when deciding which drug to prescribe. In addition, the majority of drugs require dose adjustments across patient subgroups, usually determined [...] Read more.
Tamoxifen remains a cornerstone of treatment for patients with oestrogen-receptor-positive breast cancer. Tamoxifen efficacy depends on the biotransformation, predominantly via the cytochrome P450 2D6 (CYP2D6) isoform, to the active metabolite endoxifen. Both genetic and environmental (drug-induced) factors may alter CYP2D6 enzyme activity directly [...] Read more.