Childhood Cancer

Childhood Cancer

Different responses to medications

Children’s bodies have a wide range of responses to medications, some of which are due to their genes. Some children inherit genes that do not allow them to break down (metabolize) certain drugs, or that allow them to break the drugs down very slowly. If a child cannot metabolize a drug or metabolizes it slowly, the drug can build up in the blood stream and cause excessive toxicity.

In addition, the tumor cells in individual children also vary dramatically in how they respond to different chemotherapy drugs. The tumor cells in one child’s body might be extraordinarily sensitive to a specific chemotherapy drug, while the tumor cells in another child’s body might be very resistant to that same drug.

Therefore, the combination of variability in children’s ability to metabolize drugs and variability in how sensitive their tumor cells are to certain drugs causes a big range in the effectiveness of standard doses of medications. How much of this variability is due to genetics is not well understood. However, researchers are identifying ways to test children’s ability to metabolize certain drugs and are tailoring treatments based on that genetic information. This area of science is called pharmacogenetics. Following are two examples of genetic characteristics that are used by doctors to tailor treatments to a child’s unique genetic makeup.

CYP2D6. A genetic variation currently being investigated concerns the CYP2D6 gene, which affects the metabolism of codeine. Approximately 10 percent of people do not get pain relief from codeine, because they are genetically unable to metabolize the codeine into morphine. Because codeine products are often used for painful side effects of treatment (e.g., vincristine neuropathy), some institutions test all children with cancer for this genetic variation so appropriate pain medications can be prescribed.

Methlyenetetrahydrofolate reductase (MTHFR). The chemotherapy drug methotrexate is used to treat some children with solid tumors. A common genetic variation (called MTHFR C677T) increases some children’s sensitivity to methotrexate, resulting in liver toxicity, excessively low blood cell counts, and other side effects. Children who have these reactions while receiving methotrexate are sometimes tested for this genetic variation.