Pharmacogenetics (PGx), the application of genetic variation to understand variability in medicinal response, has been heralded as the facilitator of personalized medicine and targeted therapies with the potential to alter the healthcare landscape. Key benefits of PGx tools include:
· Reducing adverse reactions, enabling selection of optimal therapy, and increasing patient compliance
· Enabling development of safer, more effective drugs
· Capable of reviving drugs that failed clinical trials or were withdrawn from the market
· Reducing time, cost, and failure rate of clinical trials
In recent years, it has become increasingly apparent that dozens of human drug metabolism polymorphisms exist and that inter-individual variability in drug metabolism is caused by these polymorphisms. Differences in drug responses can be attributed to differences in genes that code for the production of drug-metabolizing enzymes, drug transporters, or drug targets.
Variations in genes coding for key enzymes such as P450, N-acetyl-transferases, vitamin-K-metabolizing enzyme, glutathione-S transferase, and dehydrogenases lead to decreased or increased metabolism of drugs.
PGx tests that measure these variations are capable of reducing adverse reactions associated with most blockbuster drugs and helping physicians select optimal therapy and the most-effective dosage for various subpopulations. For example cytochrome P450 tests provide critical information on individual dosing and therapeutic efficiencies of drugs such as antidepressants, antipychotics, anticoagulants, anti-arrthymics, b-blockers, and oncologics.
PGx tests correlate with clinical factors, such as disease state, prediction of future disease states, drug response, and treatment prognosis, to help physicians individualize treatment for each patient.
Oncology was the first beneficiary of PGx testing, but another area that is now benefiting from PGx tests as well is antiretrovirals. For example, PGx tests to quantify HIV disease progression and tests that measure variations in various genes are playing a crucial role in development of new HIV inhibitors that are tailored to the subset of patients who respond.