The field of pharmacogenomics, also called pharmacogenetics, studies how our inherited genes affect the way we respond to drugs. The way our bodies process and handle drugs can make these drugs more or less effective, or more or less safe. A drug may respond differently in one person than another person taking the identical drug for the same condition. Also, some people may experience severe side effects from a drug, while others do not.

Pharmacogenomics now has limited use in the treatment of people with cancer, but its growth may lead to the development of more tests that doctors may give patients before starting a drug therapy. These tests are designed to analyze a patient’s genetic content to help predict whether a drug and its dosage will be safe and effective.

Many drugs that treat cancer are not fully active in the form in which they are given. They need to be “turned on,” or activated, by enzymes (proteins that speed up chemical reactions in the body) to help treat the cancer. Each person inherits variations in these enzymes that affect how fast or slow these drugs are converted. If a person’s genes are “slow metabolizers,” or slow to break down the drug, then the body doesn’t make enough active form of the drug, and the treatment may not work as well. Drugs also need to be “turned off,” or deactivated, after the cancer is treated to limit exposure to healthy tissues and reduce side effects. If a person’s enzymes that deactivate drugs are “slow metabolizers,” then very high levels of the unconverted drug remain in the body for a long time and can increase the side effects of the drug.

Genetic testing is already used to help predict whether some cancers are more likely to develop in people. For example, women with a variation in the BRCA1 or BRCA2 gene are at greater risk of developing breast and ovarian cancer, and men with BRCA1 and BRCA2 mutations are at increased risk of breast and prostate cancer. The results of these genetic tests may prompt some people to have additional cancer screenings, make lifestyle changes to avoid other risk factors, and choose preventive treatment, such as chemoprevention. Pharmacogenetic testing, however, is used for patients diagnosed with cancer and other diseases to help target the safest and most effective dose of a drug.

Pharmacogenomics offers important benefits, including:

Improving patient safety. It is estimated that severe drug reactions cause over 2 million hospitalizations each year. Pharmacogenetic testing may help identify patients who are likely to experience dangerous reactions to drugs beforehand, thereby improving patient safety and saving lives.

Improving health care costs and efficiency. The time and resources that doctors and patients spend on finding appropriate medications and doses is likely to decrease as pharmacogenetic tests are developed.

Pharmacogenomics may lead to “personalized medicine” because it has the potential to offer cancer therapy that is individually tailored to a person or a group of people based on their genetic makeup. Most drugs are currently developed to be effective for the greatest number of people possible, often referred to as the “one size fits all” approach. However, it’s not possible to identify the patients that will not benefit from a drug, or those who will experience dangerous side effects from a drug until they take it. Pharmacogenomics may decrease the use of this “trial and error” approach.

Although pharmacogenomics holds promise in helping to predict the results of drug therapy, other variables may influence how a person reacts to a drug, such as age, gender, disease severity, lifestyle habits (diet, smoking, alcohol consumption), other medications a person is taking, and environmental factors, such as exposure to pollution and toxins.

Challenges to pharmacogenomics

There are some challenges in the development and practical use of pharmacogenomics. Many doctors now do not widely practice pharmacogenomics when treating patients since the field is still new. Pharmacogenetic testing is also expensive, and insurance plans may not cover the costs of available tests. Researchers are working to develop more efficient and less expensive testing methods. Although federal legislation has been passed that makes it illegal for companies and insurers to discriminate against people based on their genetic information, some ethical, legal, and privacy issues remain unresolved, which may affect the continued development of pharmacogenomics.

Pharmacogenetic testing in practice

Here are some examples of where pharmacogenomic testing is now in use in treating people with cancer:

Colorectal cancer. Irinotecan is a type of chemotherapy commonly used for the treatment of colorectal cancer. In some people, genetic variations cause a shortage of the UGT1A1 enzyme, which is responsible for the body’s metabolism (breakdown) of irinotecan. Higher levels of irinotecan remain in the body in people with lower levels of this enzyme, which leads to severe and potentially life-threatening side effects. Doctors may use a pharmacogenomic test, called the UGT1A1 test, to see which patients have this genetic variation, and can prescribe a lower dose of irinotecan for patients with the genetic variation.

Acute lymphoblastic leukemia (ALL). Doctors also use pharmacogenomic testing for children with acute lymphoblastic leukemia (ALL). Genetic variations in an enzyme called thiopurine methyltransferase (TPMT) are found in about 10% of these children. TPMT is responsible for the metabolism of chemotherapy that is used to treat ALL. To avoid severe side effects, children with lower levels of TPMT are treated with lower doses of these drugs.

Fluorouracil (5-FU, Adrucil) chemotherapy. This drug is used to treat several types of cancer, including colorectal, breast, stomach, and pancreatic cancers. A genetic variation in some people causes them to have lower levels of the enzyme called dihydropyrimidine dehydrogenase (DPD), which helps the body metabolize 5-FU. Doctors may use a pharmacogenomic test to detect this variation in patients and to lower the dose of the drug to avoid serious side effects in these patients.

Questions to Ask the Doctor

Talk with your doctor to find out more about how your genetic makeup may affect your body’s response to a specific drug when discussing your treatment options. Consider asking the following questions:

• Would you explain my treatment options?
  
  
• Which treatment, or combination of treatments, do you recommend? Why?
  
  
• What are the possible side effects of this treatment?
  
  
• Is there a method to predict beforehand how my cancer will respond to this drug, or predict whether I might experience severe side effects?
  
  
• What are my options if the cancer does not respond to the drug, or if I suffer from severe side effects?
  
  
• Whom do I call for questions or problems?

More Information

Cancer Advances: Personalized Cancer Medicine: Translating Breakthroughs in Biology to Better Treatment

Additional Resources

American Medical Association: Pharmacogenomics

National Institute of General Medical Sciences: Frequently Asked Questions About Pharmacogenetics