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The Basis of Pharmacogenomics
Genetic differences—such as polymorphisms in genes that code for enzymes and other active proteins—can play a highly influential role in determining how individuals respond to drugs. Variance in an enzyme which happens to be a drug target often causes people with rare genetic differences in the gene coding for the enzyme to have unexpected, even harmful side effects after taking the drug,
The field of pharmacogenomics is based on the idea that examining and understanding the way drug reactions are influenced by genetic variance can lead to improvements in designing and improving drugs, and in designing individualized treatment regimes for patients.
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Improvements in drug discovery, design, and development are obvious applications for pharmacogenomics. A deeper understanding of the genetic factors which cause variance in drug metabolism can aid in the design of drugs with improved potency, reduced toxicity, and fewer side effects.
For example, pharmacogenomics can identify potential drug targets (targets are typically enzymes or other proteins), and determine which targets are least prone to genetic variance. By selecting drug targets which are not prone to genetic variance, drug designers can create drugs which are more likely to have standard, expected, and safe reactions in people who take it.
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One area of pharmacogenomics study of particular importance is how metabolism of drugs in unintended ways can cause what are known as adverse drug reactions. These occur in individuals with genetic polymorphisms in drug targets. Taking the drug causes them to metabolize it in ways which are potentially harmful.
Adverse drug reactions are a remarkably prevalent problem, causing an estimated 100,000 deaths, and a further two million major or minor health problems every year in America alone. Studies have shown that most drugs which cause adverse reactions are metabolized by enzymes with genetic polymorphisms. Identifying polymorphisms and redesigning drugs to accommodate them could improve the safety and efficacy of these drugs.
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Pharmacogenomics can also be useful in clinical trials for drugs which have passed through the approval process sufficiently that human trials are possible.
Using this approach, a technique called genostratification can be used in selecting participants for clinical trials. This means that clinicians use genetic typing to select participants who are genetically more likely to react positively to the treatment which is under study.
This can potentially allow for an improved level of treatment success, and means that “proof of concept” can be achieved sooner. This technique can also allow for a reduction in the required sample size for the trial, or shortened trial duration. Ultimately, a drug which may help save or improve lives can be used in the general public more quickly than otherwise would be possible.
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Finally, applying pharmacogenomics to patient treatment can help devise individualized treatment regimes, to ensure that patients receive the drugs which are most appropriate for their genetic makeup.
In particular, this approach has significant potential in treating cancer, because there is a great degree of variance in the way people react to chemotherapy drugs. Tumors themselves are highly variable in genetic terms, and this partially accounts for the variance in drug responses. Using an approach which individualizes treatment regimes, to accommodate for this variance could improve cancer treatments significantly.
Pharmacogenomics is useful in general for patient treatment because it has the potential to identify on an individual basis the drugs which might cause adverse reactions. A person who might experience such a reaction can then be prescribed an alterative drug.