Pharmacogenomics: Historical Perspective and Current Status
Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, United States Food and Drug Administration, Silver Spring, MD, USA.Methods in molecular biology (Clifton, N.J.) (Impact Factor: 1.29). 07/2013; 1015:3-22. DOI: 10.1007/978-1-62703-435-7_1
Pharmacogenomics and its predecessor pharmacogenetics study the contribution of genetic factors to the interindividual variability in drug efficacy and safety. One of the major goals of pharmacogenomics is to tailor drugs to individuals based on their genetic makeup and molecular profile. From early findings in the 1950s uncovering inherited deficiencies in drug metabolism that explained drug-related adverse events, to nowadays genome-wide approaches assessing genetic variation in multiple genes, pharmacogenomics has come a long way. The evolution of pharmacogenomics has paralleled the evolution of genotyping technologies, the completion of the human genome sequencing and the HapMap project. Despite these advances, the implementation of pharmacogenomics in clinical practice has yet been limited. Here we present an overview of the history and current applications of pharmacogenomics in patient selection, dosing, and drug development with illustrative examples of these categories. Some of the challenges in the field and future perspectives are also presented.
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ABSTRACT: Pharmacogenomics explores one drug's varying effects on different patient genotypes. A better understanding of genomic variation's contribution to drug response can impact 4 arenas in heart failure (HF): (1) identification of patients most likely to receive benefit from therapy, (2) risk stratify patients for risk of adverse events, (3) optimize dosing of drugs, and (4) steer future clinical trial design and drug development. In this review, the authors explore the potential applications of pharmacogenomics in patients with HF in the context of these categories.Heart Failure Clinics 10/2014; 10(4). DOI:10.1016/j.hfc.2014.07.007 · 1.84 Impact Factor
- Pharmacogenomics 03/2015; 16(4):299-301. DOI:10.2217/pgs.14.184 · 3.22 Impact Factor
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ABSTRACT: Recent studies have been established high degree of genetic diversity in solid organ tumors among individuals and even between individual tumor cells. This intratumor and intertumor genetic diversity results in a heterogeneous tumor with unique characteristics which potentially allows effective drug therapy. The goal of pharmacogenomics is to elucidate the genetic network(s) that underlie drug ef fi cacy and drug resistance. Advances in targeted and personalized therapy play an increasingly important role in many common cancers, notably lung cancer, due to the high incidence, prevalence, mortality and the greater tendency towards drug resistance seen in these patients. Non-small cell lung cancer (NSCLC) is characterized by mutations in the epidermal growth factor receptor (EGFR) and or downstream kinase pathways. This has led to the development of highly selective monoclonal antibodies and EGFR tyrosine kinase inhibitors (EGFR-TKIs) to prevent cancer initiation, proliferation, differentiation, angiogenesis, survival, and invasion. However, resistance to many of these new treatments is induced and further pharmacogenomic analysis has revealed mutations associated with increased or reduced drug ef fi cacy. Combinations of kinase inhibitors or potentially the targeting of cancer stem cells may further increase the success of pharmacogenomics in treating patients with lung cancer.European Journal of Pharmacology 06/2015; · 2.53 Impact Factor
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