WEDNESDAY, Aug. 4, 2004 (HealthDayNews) -- Researchers have identified a set of genes that makes some children resistant to the drugs used against acute lymphoblastic leukemia (ALL), the most common childhood cancer.
The finding could be an important step toward the goal of making the disease curable, according to the Tennessee researchers.
ALL accounts for 23 percent of cancer diagnoses in children aged 15 and younger. About 80 percent of the 3,000 U.S. children diagnosed with the disease each year can be cured by combination drug therapy, but that treatment fails in the other 20 percent of cases.
Now physicians at St. Jude Children's Research Hospital in Memphis report they have identified 124 genes that cause resistance to the four most widely used drugs against ALL. Their finding came from detailed genetic studies of 271 patients treated at St. Jude's and other hospitals.
The study appears in the Aug. 5 issue of the New England Journal of Medicine.
"This provides a target for developing new agents that inhibit the products of the genes that are turned on in resistance," said study author William E. Evans, scientific director at St. Jude. "We are putting all the data in the public domain as of tomorrow. We hope that many laboratories around the world will get focused on these genes to take the science further."
Evans said he and his colleagues are extending their work, looking for genes associated with resistance to other drugs used to treat ALL. "We looked at four drugs, and patients sometimes are treated by eight to 10," he explained.
One goal of the research is to find out "how do we get to the last 20 percent of patients," Evans said. But another hope is that genetic analysis can identify drugs that would not be effective in a given patient, to reduce the side effects that go along with drug therapy.
The kind of genetic analysis described in the journal report now is being done on all ALL patients at St. Jude, Evans said, but those analyses are not used to make decisions on treatment.
"We have to take one step at a time," he said. "The next step is to verify the findings of the current study. We're also searching in the laboratory for new drugs."
Dr. William L. Carroll is professor of pediatrics at New York University School of Medicine and Mount Sinai School of Medicine in New York City. He co-authored an accompanying editorial in the journal.
The St. Jude report is "the first of a number of investigations designed to provide insight into the mechanisms of drug resistance. These will give us the tools needed to design better drugs and apply current drugs more effectively," he said.
Cancer drugs inevitably have side effects that a genetic analysis could help reduce in a given patient, Carroll said. "By getting a comprehensive genetic fingerprint, we could tailor therapy," he said. "We would like to give just enough medicine, with intensive therapy for those patients who have a high risk of recurrence."
For this one malignancy, the idea of a cure for cancer now seems possible, the physicians said.
"Three of every four children are now cured," Carroll said. "Now the goal is to close that gap. This study represents a step in that direction."
More information
The National Cancer Institute has more about acute lymphoblastic leukemia and its treatment.
