Treatment Tailored to Fit: New Tool Evaluates Genes to Predict Best Therapy for Brain Tumors

Every year, nearly 2000 children are diagnosed with brain tumors. Their odds for recovery are much lower than those for many other childhood tumors. Even if treatment is successful, they may face devastating—and lifelong—disabilities because of their toxic mix of chemotherapy. At the Baylor College of Medicine, Dr. M. Fatih Okcu is determined to improve the outcome for these kids—and give them their best chance for a cure without complications.

"Brain tumors account for approximately one third of all childhood cancer diagnoses," Okcu says. "And while we can save nearly 60 percent of these children, many will suffer long term side effects as a result of their therapy."

The majority of children with brain tumors will have surgery, followed by radiation, chemotherapy or a combination of both. Some will do well. Others will suffer complications such as profound hearing loss, learning problems, second cancers—even death.

"We don't yet know which children will benefit from radiation, or which will do better with a regimen of chemotherapy after surgery. And we don't have a tool to help us predict which children are more likely to suffer serious side effects as a consequence of treatment," adds Okcu.

Today, all children with the same type of brain tumor undergo the same treatment regimen, despite our understanding that "one size does not fit all." That is why Okcu, a pediatric oncologist and a Hope Street Kids' funded researcher, is working hard to develop a tool that will help identify a patient's best therapeutic option.

Okcu believes the answer lies in genetic variations that influence how an important family of enzymes, called glutathione-s-transferases or GST enzymes, functions in individuals. These enzymes, are responsible for metabolizing chemotherapuetic drugs that are used to treat brain tumors and control the body's reaction to dangerous free radicals that result from radiation.

"We know that because of 'genetic polymorphisms,' GST enzymes function differently from one patient to the next," Okcu says. In some people, these enzymes will break down chemotherapy drugs in the body in the proper and expected way, allowing the drugs to reach tissues and destroy cancer cells. In other patients, the drugs are metabolized in an exaggerated fashion, resulting in less effective treatment. While the former group of patients is expected to have a higher toxicity, the latter group will have a less successful treatment.

"Understanding the differences in how these enzymes function from one patient to the next can provide a clue [as] to which treatment option is best," says Okcu. "Treatment then becomes more tailored-and ultimately much more effective."

Okcu is compiling information from 175 children with brain tumors who have already completed treatment. He is correlating outcomes, treatment and genetic variations for three types of GST enzymes, and is hoping to find a trend.

"When we learn which genetic variation results in [a] favorable outcome from which therapy, and which appears to predispose patients to side-effects, we will have an effective predictive tool," says Okcu. "Then patients can be tested at the time of diagnosis, providing oncologists with a guideline for treatment."

"We hope to package the tool in an easy-to-use kit that uses computer genetic array analysis to produce a profile of each patient and his [or her] best treatment option!"

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