Pharmacogenomics steps toward
Hong-Guang Xie1† &
Felix W Frueh2
1Vanderbilt University School
Division of Clinical
Departments of Medicine and
Nashville, TN 37232–6602,
2US Food & Drug
Center for Drug Evaluation
Office of Clinical
1451 Rockville Pike,
HFD-860, Room 2040,
Rockville, MD 20852, USA
dosage, targeted therapy
The goal of personalized medicine is to maximize the likelihood of therapeutic efficacy and to minimize the risk of drug toxicity 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. This review collates a variety of examples that have great potential for immediate and effective introduction into clinical practice. In addition, other exploratory examples with a particular focus on drug safety and targeted cancer therapy are summarized.
During the past decade, in particular after the
completion of the Human Genome Project [1,2],
an explosion of information regarding genetic
susceptibility to complex diseases and genetic
variability in drug responses was observed.
Genomics has become an integral part of modern drug development, and a large number of pharmaceutical companies are using this information to identify novel drug targets, identify patient subpopulations that are likely to benefit
from the therapy under development, or for
other screening purposes. While this new knowledge has led to concrete clinical advances, it has also led to speculation about the projected benefit from pharmacogenomics for the individual patient: what has been missing was the effective
translation of this information into clinical practice. Even though several reasons exist as to why this hasn’t happened yet, one major issue is the
lack of provision of effective information regarding the benefit of pharmacogenomics to physicians and patients. Should true personalized medicine become the reality that is hoped for,
pharmacogenomics needs to become fully integrated into the strategy of identifying the best possible drug therapies for the prevention, diagnosis and treatment of disease. However, a genetic or genomic profile alone will, only in rare
occasions, be a definite determinant of therapy:
other factors such as age, gender, body mass, or
potential drug–drug interactions need to be considered as well, leaving the burden of making an educated, clinical decision about treatment in
the hands of physicians. However, pharmacogenomics, the science of how an individual’s
10.2217/174105220.127.116.115 © 2005 Future Medicine Ltd ISSN 1741-0541
genetic makeup influences a person’s reaction to
drugs, can greatly improve this decision-making
process by providing critical insights into how
this patient will react to the treatment of choice.
Current status of drug therapy
The safety and efficacy of a drug is evaluated
according to strict regulatory guidelines before
the drug is marketed. However, it is impossible
for an approved drug to be safe or effective for
everyone. Genetic and environmental factors,
including their interactions, result in substantial...
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