Inhibiting a particular cancer-causing gene can enhance the cell-killing effects of radiation, a team of radiation oncologists and cancer biologists at the Kimmel Cancer Center at Thomas Jefferson University in Philadelphia has found.
Adam Dicker, M.D., Ph.D., professor of radiation oncology at Jefferson Medical College and his co-workers used an increasingly common animal model, the zebrafish, and antisense technology to show that the drug flavopiridol works by blocking the activity of the gene, cyclin D1, which is made in excessive amounts in about half of all breast cancers. Using similar techniques in the future, the scientists say, may enable researchers to better gauge the effects of drugs.
According to Dr. Dicker, flavopiridol was found to inhibit cyclins, a family of genes vital to cell functioning. When it was initially tested in clinical trials, it was found to be toxic in humans. But in the laboratory, it added to the cell-killing effects of ionizing radiation, which is used to treat cancer. No one was sure why.
To find out, Dr. Dicker and his group turned to zebrafish. If they understood how the drug was causing toxicity, they or someone else could potentially design molecular copycat drugs that worked just as well, but were less toxic.
"Zebrafish enabled us to add a vertebrate system to examine both efficacy and toxicity issues," he notes. They report their findings November 7, 2006 at the annual meeting of the American Society for Therapeutic Radiology and Oncology in Philadelphia.