Doctors have long known that people sometimes differ in how a drug works in their bodies. The field of pharmacogenetics (or pharmacogenomics) focuses on how genes affect the way people respond to medications. The idea is to create specific medications that will be effective in people with a certain gene while sparing use—including the potential side effects of use—in people without the gene. The ultimate goal is to match drugs to unique genetic profiles.
The genes of many cancers differ from noncancer genes in the same individual. These cancer genes are often very active, providing scientists with targets for effective cancer treatment. For example, the cancer drug trastuzumab is prescribed to treat metastatic breast cancer in which the tumors contain an overactive HER-2 gene. It is estimated that nearly 30% of all women with breast cancer have tumors with this type of abnormal gene activity. If doctors can determine excessive HER-2 activity in a tumor, trastuzumab can be used to block the effects of the HER-2 gene and improve cancer survival. While trastuzumab can be lifesaving in some, it also has serious potential side effects which must be balanced against its benefits.
Likewise, the drug imatinib is used in people with chronic myeloid leukemia whose cancers have a gene that makes an abnormal leukemia-causing protein, BCR-ABL. This medication may also be effective in treating other types of cancer that affect the blood cells, as well as gastrointestinal stromal tumors.
Identifying Natural Variations
Even though we all have the same overall number of genes, what contributes to our individuality, including our susceptibility to disease and reactions to medications, are the unique variations within our own set of genes. These are naturally occurring differences, known as single nucleotide polymorphisms (SNPs). Among the more than 3 billion pairs of DNA building blocks in the human genome, a very small fraction of these pairs vary from person to person. Yet these genetic variations are at the heart of pharmacogenetics research.
By digging deeper into our molecular blueprints, medication will become more tailored to groups or individuals with certain genetic flags. Scientists hope that understanding these genetic variations will increasingly explain individual differences in the way that drugs are absorbed and metabolized, their side effects, and their overall effectiveness. Some of this understanding has begun to find its way into clinical applications.
For example, AmpliChip CYP450 is a test that measures variations in 2 genes that play a role in the metabolism of some commonly prescribed drugs. The test’s manufacturer claims AmpliChip can reduce the chances of unwanted drug reactions if doctors use it to guide their prescriptions of drugs known to be metabolized through 1 of the 2 measured genes. Test results may also allow dosages to be adjusted for those persons whose genes lead them to metabolize drugs unusually rapidly or unusually slowly.
Earlier Diagnosis, Tailored Treatment
Advances in molecular analysis offer the promise of improvements not only in individualized treatment, but also in early disease diagnosis, as well. If researchers know the genes or gene products to look for, diseases may be found earlier, potentially even before symptoms are apparent or the disease process really gets going—an obvious advance in the case of monitoring for recurrent cancers, for example.
The Oncotype DX Breast Cancer Assay is a panel test designed to detect the presence of 21 cancer-related genes. The National Cancer Institute is currently doing a large study involving over 7,000 women with early stage breast cancer. The researchers are studying whether certain genes that are linked to cancer recurrence can be used as a basis to select individualized treatment plans for the best outcomes.
Personalized medicine may be able to:
- Identify people at risk for disease
- Provide earlier intervention—Researchers hope that quicker treatment may translate into more effective treatment and better outcomes.
- Develop better drugs more quickly—As scientists understand the genetic variations and molecular pathways involved in a disease, pharmaceutical companies hope to develop highly targeted drugs more quickly than is the norm today.
Before personalized medicine can be widely applied, however, much more research is needed in the field of pharmacogenetics.
National Institute of General Medical Sciences
Personalized Medicine Coalition
Public Health Agency of Canada
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Last reviewed April 2017 by Michael Woods, MD, FAAP Last Updated: 3/16/2015