Chapter 1: Introduction and Fundamentals of Pharmacogenomics

INTRODUCTION

OVERVIEW AND HISTORY

Historical Perspective of Precision Medicine

In 2015, President Barack Obama announced the launch of the Precision Medicine Initiative in his State of the Union address to the nation. The mission of the initiative is “to enable a new era of medicine through research, technology, and policies that empower patients, researchers, and providers to work together toward development of individualized care.”¹ The term “personalized medicine” has also been used to describe this individualized care; however, the term “precision medicine” is favored so as not to presume that the care that patients will receive will differ from each other.¹

In this new era of precision medicine, treatment and prevention of disease are tailored to the individual. Such individualization contrasts with traditional approaches to care, which have largely relied on “one-size-fits-all” models. Individualized care considers unique characteristics of individuals, including past medical history, family history, lifestyle, diet, microbiome, and genome sequence. Pharmacogenomics uses the individual’s genomic sequence to predict drug response and is essential to achieving the mission of precision medicine. However, the science and art of prescribing pharmacotherapy are not perfect.

As mentioned, the selection of drug therapy has largely relied on the “one-size-fits-all” approach due to the homogeneity commonly seen in clinical trials leading to the approval of new drugs by the U.S. Food and Drug Administration (FDA). Furthermore, diverse responses to drug therapy are often not observed until postmarketing use, which can characterize and stratify drug response to the uniqueness of individuals rather than strict inclusion and exclusion criteria of the randomized, placebo-controlled clinical trial. Many individuals will fail pharmacotherapy at first, and some individuals will trial two or more unique drugs before finding effectiveness with minimal adverse effects. Pharmacogenomics enters here with the promise of predicting drug response for better clinical outcomes and less adverse events. As the data supporting specific gene–drug pairs grow, we can expect that pharmacogenomics will lead to more actionable changes to prescribing that meet the mission of the Precision Medicine Initiative.

Advances in Technology Leading to the Present State of Precision Medicine

In 1990, the Human Genome Project, an international research endeavor coordinated by the U.S. National Institutes of Health and the U.S. Department of Energy, set out to sequence a complete and accurate sequence of the human genome and to locate the exact location of an estimated 20,000 to 25,000 human genes. Fourteen years later, the sequencing of the first entire human genome was completed, including more than 3 billion DNA base pairs, and made publicly available for others to build upon the work.² This complete sequence of the human ...