Drug Target Pharmacogenomics
- PDF / 182,777 Bytes
- 11 Pages / 612 x 790.56 pts Page_size
- 96 Downloads / 205 Views
Am J Pharmacogenomics 2001; 1 (4): 271-281 1175-2203/01/0004-0271/$22.00/0 © Adis International Limited. All rights reserved.
Drug Target Pharmacogenomics An Overview Julie A. Johnson Departments of Pharmacy Practice and Medicine (Cardiology), University of Florida, Gainesville, Florida, USA
Contents Abstract 1. Drug Target Pharmacogenetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.1 Associations Between Direct Drug Target Polymorphisms and Drug Efficacy/Toxicity . . . . . . . . . . . . . . . 1.2 Associations Between Polymorphisms of Signal Transduction/Downstream Proteins and Drug Efficacy/Toxicity 1.3 Associations Between Polymorphisms of Disease Pathogenesis Proteins and Drug Efficacy/Toxicity . . . . . . . 2. Limitations of Current Pharmacogenetics Literature and Need for a Genomics Approach . . . . . . . . . . . . . . 2.1 Inability to Adequately Predict Response/Toxicity Based on Genotype . . . . . . . . . . . . . . . . . . . . . . . 2.2 Inconsistencies Between Pharmacogenetic (Single Gene) Studies . . . . . . . . . . . . . . . . . . . . . . . . . 3. Genomic Approaches to Describing Drug Response Variability . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1 Candidate Gene Approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.2 Genome Scanning Approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4. Use of Pharmacogenomics in Drug Discovery and Drug Development . . . . . . . . . . . . . . . . . . . . . . . . . . 4.1 Mapping New Drug Targets . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.2 Improving the Efficiency of Drug Development . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5. Clinical Potential for Pharmacogenomics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Abstract
. . . . . . . . . . . . . .
. . . . . . . . . . . . . .
. . . . . . . . . . . . . .
. . . . . . . . . . . . . .
. . . . . . . . . . . . . .
. . . . . . . . . . . . . .
273 273 274 274 275 275 276 277 277 277 278 278 278 279
Pharmacogenomics is a field aimed at understanding the genetic contribution to variability in drug efficacy and toxicity. The goal is to be able to select the drugs with the greatest likelihood of benefit and the least likelihood of harm in individual patients, based on their genetic make-up. Pharmacogenetics has historically been a field focused primarily on genetic polymorphisms in drug metabolizing enzymes and their impact on drug efficacy and toxicity. More recently, investigators have begun to study the relationship between drug target polymorphisms and drug efficacy and toxicity. There are now numerous examples in the literature of associations between drug target polymorphisms and drug effect. Drug targets can be broken into three main categories: the direct protein target of the drug, signal transduction cascades or
Data Loading...
