Pharmacogenomics: Promises and Problems

Pharmaceutical researchers took great interest in the Human Genome Project in the hopes that mapping the human genome would allow them to develop drugs and diagnostic tests tailored to the metabolic idiosyncrasies of individual patients, ushering in an era of "personalized medicine." But so far, pharmacogenomics, the study of the effects of an individual’s genetic makeup on his or her response to drugs, has not produced the hoped-for revolution in the pharmaceutical industry, for two primary reasons: roadblocks in obtaining approval and the very high cost of molecular testing. In general, reimbursement has lagged behind technological developments, but these problems are nothing new, having plagued the field of molecular diagnostics for years. Nevertheless, the promise of pharmacogenomics is very real. Already, the FDA has approved at least one DNA microchip array that can test for variations in enzymes that metabolize the breast cancer drug tamoxifen and will allow doctors to adjust doses and treatment regimens accordingly, Paul R. Billings, MD, PhD, said in a session at the annual meeting of the American Society for Clinical Pathology in October.

Genetic variations govern an individual’s ability to metabolize drugs in four basic ways, explained Dr. Billings, Vice President of Biotechnology and Healthcare Strategy and Senior Geneticist, Laboratory Corp. of America Holdings (Burlington, NC). If the target genes are completely functional, the drug will metabolize normally and a complete therapeutic response with no or minimal adverse effects will be experienced. Reduced or partially functional genes result in intermediate metabolism, with a diminished therapeutic effect and possible mild side effects. If the genes do not function at all, the patient will be unable to metabolize the drug. Under this scenario, not only will patients derive little or no therapeutic benefit from the drug, they could experience serious adverse effects due to the buildup of toxic levels of the drug in the body