Introduction to Pharmacogenomics
Despite major advances in drug treatment and therapy, it is still difficult for doctors to determine the right medication and the right dose the first time for every individual patient. The chosen drug should be the most effective available for a specific person and condition with the fewest possible side effects. However, a drug may work well in one person but have no effect in another. One person may tolerate a drug well, while another suffers from severe side effects. The questions then become, how will this person’s body react to this specific drug and will this person have the capacity to benefit from this treatment?
For all major classes of drugs given at standard doses, a substantial portion of patients do not respond, respond only partially or experience adverse drug reactions. Drug concentrations in plasma can vary more than 600-fold between 2 individuals of the same weight on the same drug dosage. This variation can be of a genetic, physiological, pathophysiological or environmental origin. Adverse drug reactions represent a major problem as evidenced by a number of prominent drug safety problems and withdrawals both historic and current.
- 1950’s: Thalidomide was recalled after thousands of children were born with severe malformations.
- 2001: Cerivastatin was withdrawn from global markets due to the occurrence of rhabdomyolysis, a severe musculoskeletal side effect which was sometimes fatal.
- 2004: Rofecoxib was withdrawn globally because of an estimated 100,000 extra thrombotic events associated to this drug’s usage in the US.
- 2008: Rimonabant, an anorectic anti-obesity drug aimed at reducing appetite, was withdrawn from the market after it was associated with increased risks of severe suicide and depression.
- 2009: Efalizumab, an immunosuppressant used to treat psoriasis, was withdrawn from the market due to increased risks of progressive multifocal leukoencephalopathy, a brain infection caused by the reactivation of a latent JC virus.
Genome variability has now been recognized to be an important contributor to the variability in drug response. Using genetics and genomics, researchers are now beginning to identify genes and gene mutations that play key roles not only in disease development but also in how a person will react to a given drug.
Pharmacogenetics: investigates a single gene or polymorphism, describes the influence of genes on the efficacy and side effects of drugs
Pharmacogenomics: investigates the entire genome, serves as a tool to identify new targets and develop new drugs, studies interactions between drugs and the genome
Medical genomics is the correlation of individual differences in gene structure and function with the characteristics of disease and response to treatment. This revolutionary area of research promises to fundamentally change the practice of medicine by not only facilitating the identification of new genes with disease relevance and providing better characterization of subcategories of disease but also creating the potential for individualized drug therapies.