Chapter 7: Pharmacogenomics

Abstract

There is great variation in drug-response phenotypes, and a “one size fits all” paradigm for drug delivery is flawed. Pharmacogenomics is the study of how human genetic information impacts drug response, and it aims to improve efficacy and reduced side effects. In this article, we provide an overview of pharmacogenetics, including pharmacokinetics (PK), pharmacodynamics (PD), gene and pathway interactions, and off-target effects. We describe methods for discovering genetic factors in drug response, including genome-wide association studies (GWAS), expression analysis, and other methods such as chemoinformatics and natural language processing (NLP). We cover the practical applications of pharmacogenomics both in the pharmaceutical industry and in a clinical setting. In drug discovery, pharmacogenomics can be used to aid lead identification, anticipate adverse events, and assist in drug repurposing efforts. Moreover, pharmacogenomic discoveries show promise as important elements of physician decision support. Finally, we consider the ethical, regulatory, and reimbursement challenges that remain for the clinical implementation of pharmacogenomics.

PharmGKB: A worldwide resource for pharmacogenomic information

“…In the context of PGx, this means the focus is on genes coding for the direct targets of the drug, as well as any gene-products affected downstream or responsible for the clinical outcome 19 .…”

System pharmacogenomics application in infectious diseases

“…The aim is to derive a systemic view of the possible interactions a drug may have. This helps to understand not only the effect of drug but also the associated side effects of a drug by looking at the effects of a drug in context of cellular networks as well as exploring relationships between drugs [10,11]. Thus the individual patient susceptibility and the side effects can be accounted for and the off-target effects can be reduced.…”

Concept of Pharmacogenomics and Future Considerations

“…It has always been unethical to give placebo or inferior treatment to diseased individuals in the presence of better available therapeutic options. In this direction, validation of genetic data in clinical trials may be much more difficult with limited experimental data and lower predictive performance of the genetic markers in laboratory-based studies [7]. Nonreplicability of detected associations is another major limitation of pharmacogenomic studies.…”