ADVANCEMENTS IN PHARMACOGENOMICS AND TAILORED MEDICATION THERAPIES
Abstract
Since genetic variation in pharmacokinetic and pharmacodynamics processes intimately affects drug response and toxicity, interest in integrating pharmacogenomics with the field of nanomedicine has steadily increased. Indeed, the genetic code of an individual may in the future become a standard diagnostic to tailor the use of new medication therapies. This review combines the most recent knowledge regarding pharmaco- and toxicogenomics for a variety of drugs and drug targets with perspectives on emerging technological platforms in nanomedicine. The aim is to create improved guidance complementing drug development and clinical application of nanotherapeutical approaches on an individual basis (M. Lauschke et al., 2019).
Therapeutic regimens feature a variety of unequal outcomes—both between individuals and in the same individual at different times. The concept of providing treatment regarding the individual genetic history of diseases and drug response has seen a massive shift forward with the accomplishment of the draft sequence of the human genome and the construction of high-throughput methodologies to analyze the human genetic code. Pharmacogenomics is focused on the understanding of specific sequence changes of the genome that can discriminate between patients that respond optimally to treatment and those who could be at risk of severe adverse effects. These genetic variant biomarkers are testimony to an optimized therapeutic approach. The impressive increase in information regarding genetic variability has led to vast improvements in the predictive potential of pharmacogenomic tests. This information can help in the determination of pharmacological-drug treatment at initiation of therapy or following therapy in the form of companion diagnostics. Pharmacogenomics concerns the occurrence of base-pair changes in single nucleotides assuring the sequence diversity of the human genome.
The genome sequence is the same in all cells but a single nucleotide polymorphism (SNP) refers to a chromosomal position where different sequences can be present in diverse individuals but not in a pair of homologous chromosomes. SNPs are the most numerous form of genetic variability and it is anticipated that three million SNPs are occurring in the human genome. However, not all SNPs are randomly spread and the majority may have no functional consequence on the proteome. For given bases, only four diverse nucleotides are possible in a nucleotide chain; and that the coding sequences, giving rise to the protein repertoire, display only three please-. Hence, it is common for SNPs having no consequence on the protein product. If a SNP is positioned in a transcription factor binding site it could affect gene regulation. The diversity and complexity of the genetic code has ramifications for the comprehension of polymorphisms of drug-metabolizing enzymes since a largely heterologous network of auxiliary proteins makes the metabolism of every drug unique.
