One of the most important components of personalized medicine is pharmacogenomics, the
study of genetic variations that influence individual response to drugs. Enzymes responsible
for drug metabolism and proteins that determine the cellular response to drugs (receptors)
are encoded by genes, and can therefore be variable in expression, activity level and
function when genetic variations are present. Knowing whether a patient carries any of
these variations may help health care professionals individualize drug therapy, decrease the
number of adverse drug reactions and increase the effectiveness of drugs. Pharmacogenomics
has been characterized as “getting the right dose of the right drug to the right patient at
the right time.”
Today, many of the complexities of human drug response are sufficiently well understood to transform the field of pharmacogenetics from a descriptive to a predictive science, leading to safer and more effective prescribing and dosing. 12 This kind of testing is being used more frequently in cancer treatment (eg, BRCA1 in breast cancer) and internal medicine (eg, VKORC1for warfarin metabolism), but only very recently in pain medicine.
The goal of personalized medicine is to maximize the likelihood of therapeutic efficacy and to minimize the risk of drugtoxicity for an individual patient.One of the major contributors to this concept is pharmacogenomics. Marked interindividual genetic variation contributes significantly to both susceptibility to diseases, and response to drugs. Even though pharmacogenomics is not a new science, the translation of pharmacogenomics into clinical practice (i.e.,personalized medicine) has not taken place at the same pace as science is delivering new results. It is felt that a large number of recent pharmacogenomic findings allow bold steps to be taken toward personalized medicine.
The aim of this (first) chapter is to overview the promises of the pioneering field of
pharmacogenetics towards personalized medicine, completely changing the present
therapeutic paradigm of Done dose fits all patientsE and Dtrial-and-errorE prescriptions to
Dmatching the right dose to the right, specific genetic signature of the patient and at the
right timeE. The review points out the evolution from pharmacogenetics to
pharmacogenomics, as well as the impact of genome-wide-associated studies (GWAS) and
next generation sequencing technologies on deciphering Dmissing heritabilityE and on
validation and approval of pharmacogenetic biomarkers as it is reflected both in regulatory
authorities recommendations and from consortia perspectives.