4. Examples of pharmacogenomics and pharmacogenetics in the clinic today

Doctors are using these new technologies to improve the efficacy of medicines and to get the optimal response in their patients. There are many examples of the successful use of pharmacogenetics and pharmacogenomics in clinical treatments. A selection is given below.

Example 1: reducing side effects (Adverse Drug Reactions, ADRs)
Possibly the most successful use of pharmacogenetics to date is the testing of HIV patients for a gene variant known as HLA-B*5701. The patients are tested for this gene before they are treated with the anti‑viral medicine ‘abacavir’. It is known that some patients (5 to 8%) will get side effects as a result of taking abacavir. The side effects can include skin rash, fever, gastrointestinal problems (stomach and gut), respiratory problems (breathing), and death. Because of this risk, some doctors have not been willing to prescribe the medicine even though it is an effective treatment for many patients with HIV. It was found that there is a link between adverse reactions and the presence of the HLA-B*5701 variant. Therefore, doctors can now test their patients for the variant before abacavir is given. There is good evidence that this testing has significantly reduced the number of adverse reactions.

Example 2: responders and non-responders

‘HER2 positive’ breast cancer cells have many extra copies of the gene that expresses the protein ‘HER2/neu’. This means that these particular cancer cells produce too much of the protein, and this causes the cells to grow and divide without control. The medicine ‘trastuzumab’ binds to the HER2/neu protein and this improves the overall survival for HER2 positive patients with advanced breast cancer (responders). The medicine does not have the same effect in patients who are not HER2 positive (non‑responders).

Example 3: dose choice

Warfarin is a medicine used to prevent abnormal blood clotting. Each patient’s blood is monitored when they are treated to ensure the correct level of warfarin has been given (enough to prevent abnormal clotting, but not so much that there is a risk of bleeding). In addition, there are guidelines now available for using pharmacogenetic tests for the enzymes known as ‘CYP2C9’ and ‘VKORC1’. CYP2C9 helps break down medicines in the body and VKORC1 plays a role in blood clotting (coagulation). The results from these tests can help the doctor choose the best start dose for any individual patient.