Pharmacogenomics in Treating Cancer

The Basics of Pharmacogenomics

Genetic variance of metabolizing enzymes is an important factor which contributes to adverse drug reactions, and can cause variance in the efficacy and safety of drugs from person to person. Genetics plays a role because a small change in the DNA which codes for an enzyme can cause that enzyme to behave differently when metabolizing a certain drug. This in turn can increase or decrease the potency of a drug, or even cause harmful and unexpected side effects.

Pharmacogenomics is an interdisciplinary science which aims to determine the contribution of genetics in the variance of response to individual drugs, and use this information to create safer, more effective pharmaceuticals.

This approach can also be used to design individualized treatment profiles for patients on a case-by-case basis. Such treatment regimes are showing promise in the treatment of certain types of cancers.

Using the Principles of Pharmacogenomics to Treat Cancer

Pharmacogenomics has enormous potential for optimizing patient responses to chemotherapy agents, because there are often enormous differences in the way people respond to these drugs. Determining why these differences are present may help researchers design new and better drugs, and use existing drugs to treat people more effectively while reducing toxic side effects.

During the past ten years, techniques for identifying genetic variation have become less expensive, less labor-intensive, and much more efficient, allowing genotyping to be performed more quickly on an individual basis.

With high-throughput genotyping technology available, pharmacogenomic analysis can be used to examine both normal and tumor cells, and match with patients the drugs which are most likely to be effective for the type of cancer they have. One situation in which this approach has been recently applied is in the detection of mutations in epidermal growthfactor receptor, which is associated with patient responses to the chemotherapeutic agent known as gefitinib. The drug targets the tyrosine kinase domain of the receptor, and acts with variable efficiency due according to whether or not the patient expresses a mutated version of the receptor.

Another area in which pharmacogenomics may prove useful is in the development of cancer drugs, and in clinical trials involving chemotherapeutic agents.

For example, pharmacogenomics can allow for the use of a technique called genostratification in selecting participants for clinical trials—that is, choosing participants who are genetically more likely to react positively to the treatment. This achieves a better level of treatment success, and means the level required for “proof of concept” is reached more quickly. This means it may be possible to reduce the required sample size, or shorten the duration of the trial, allowing a potentially useful drug to reach the public more quickly.