Pharmacogenomics could replace 'trial-and-error' with science from the human genome


Nature article from St. Jude points to challenges ahead and approaches that will be required to individualize drug therapy based on a patient's genetic make-up

(MEMPHIS, TENN.--May 27, 2004) The future use of a gene-based technology called pharmacogenomics could lower the cost of health care by decreasing the occurrence of adverse drug effects and increasing the probability of successful therapy. These findings are published by investigators at St. Jude Children's Research Hospital in the May 27 issue of Nature.

According to the authors, the significant potential for improving health and reducing cost will not be achieved unless three things happen. First, more studies must be undertaken to identify the network of genes that govern most drug responses. Second, systems must be developed to assist physicians and pharmacists in interpreting genetic tests for selecting drug therapy. Finally, legal protections must be put in place to preclude the misuse of genetic information from patients.

The science and technology of pharmacogenomics, which bases the choice of medications and their dosages on the patient's specific genetic makeup, is the basis of "individualized medicine," according to the article's co-authors, William E. Evans, Pharm.D., St. Jude Scientific director, and Mary V. Relling, Pharm.D., chair of St. Jude Pharmaceutical Sciences.

The key to pharmacogenomics is its ability to predict how a patient will respond to medications by identifying individual polymorphisms, or variations, in specific genes that contribute to that response. Pharmacogenomics can also help investigators discover more effective drugs, such as anti-cancer agents.

"Some genes are over-expressed in cancer cells that are either sensitive or resistant to anticancer agents, while other genes are under-expressed, or relatively inactive," Evans said. "Drugs designed to target the genes that are over-expressed in drug-resistant cancer cells would make logical targets for new anti-cancer drugs in an attempt to reverse this resistance."

Pharmacogenomic studies could also save potentially valuable new drugs from being abandoned during clinical trials because the medications are toxic to a small percentage of patients. Identifying the tell-tale "signature" of responses of specific genes known to occur in patients with toxic responses would allow clinicians to determine which individuals should not take the drug. This would protect patients from toxicity while allowing an otherwise effective--and perhaps life-saving--drug to be approved for use in patients who are at low risk of toxicity.

The use of pharmacogenomics in routine medical care will depend on a change in thinking among most clinicians, the authors say. Clinicians are generally educated to start treatment using an "average dose" rather than considering whether the patient might represent an exception to this rule.

"The medical and pharmaceutical communities tend to avoid trying to individualize therapy even using such simple patient characteristics as age or kidney function," Relling said. "So we've become accustomed to designing treatments using a "trial-and-error" approach. Incorporating pharmacogenomics into prescribing decisions will represent a major change for the health care community. Clinicians are reluctant to incorporate genetic information into the medical record, as long as it is not clear whether health insurance companies might discriminate against patients at high genetic risk for adverse health events."

The authors also warn that it is difficult to conduct clinical trials that prove that individualized drug therapy based on genetics actually improves outcomes. Such trials could be complicated by several factors: multiple genes might influence patient response to the drug; there might be interaction with other drugs given simultaneously; and the seriousness or rate of progression of the disease as well as diet and activities such as smoking might affect treatment outcome.

"Despite the enthusiasm researchers have for advancing biomedical technology and exploring the human genome, there is little willingness to incorporate pharmacogenomics into clinical trials," Evans said.

What is needed, according to the authors, are large-scale clinical trials that incorporate comprehensive pharmacogenomic studies. In order to bring the significant potential benefits of pharmacogenomics to the public, medical practice has to evolve from the trial-and-error approach. For that to happen, society must institute protections against misuse of genetic information. Groups with a stake in better, affordable health care must also support the initial investment needed to develop the field of pharmacogenomics and incorporate it into daily clinical practice.

Source: Eurekalert & others

Last reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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