Pharmacogenetics, pharmacogenomics, and individualized medicine.
Pharmacol Rev 2011 Jun; 63(2):437-459
Individual variability in drug efficacy and drug safety is a major challenge in current clinical practice, drug development, and drug regulation. For more than 5 decades, studies of pharmacogenetics have provided ample examples of causal relations between genotypes and drug response to account for phenotypic variations of clinical importance in drug therapy. The convergence of pharmacogenetics and human genomics in recent years has dramatically accelerated the discovery of new genetic variations that potentially underlie variability in drug response, giving birth to pharmacogenomics. In addition to the rapid accumulation of knowledge on genome- disease and genome-drug interactions, there arises the hope of individualized medicine. Here we review recent progress in the understanding of genetic contributions to major individual variability in drug therapy with focus on genetic variations of drug target, drug metabolism, drug transport, disease susceptibility, and drug safety. Challenges to future pharmacogenomics and its translation into individualized medicine, drug development, and regulation are discussed. For example, knowledge on genetic determinants of disease pathogenesis and drug action, especially those of complex disease and drug response, is not always available. Relating the many gene variations from genomic sequencing to clinical phenotypes may not be straightforward. It is often very challenging to conduct large scale, prospective studies to establish causal associations between genetic variations and drug response or to evaluate the utility and cost-effectiveness of genomic medicine. Overcoming the obstacles holds promise for achieving the ultimate goal of effective and safe medication to targeted patients with appropriate genotype.
Drugs; Drug-interaction; Drug-therapy; Pharmacodynamics; Pharmacology; Genes; Genetic-factors; Genetics; Medical-care; Medical-treatment; Metabolism; Biological-effects; Biological-transport; Diseases; Safety-measures; Regulations; Medicinal-chemicals
Q. Ma, National Institute for Occupational Safety and Health, Health Effects Laboratory Division, Toxicology and Molecular Biology Branch, MS-11-039, 1095 Willowdale Road, Morgantown, WV 26505