Derivative of protein produced by bacteria blocked cell death pathway, study finds
THURSDAY, April 10 (HealthDay News) -- A modified version of a natural intestinal protein has protected animals against the damage caused by the kind of radiation used in cancer therapy, researchers report.
A first human trial of the protective treatment could start later this year, said study co-author Andrei V. Gudkov, senior vice president for basic research at the Roswell Park Cancer Institute in Buffalo, N.Y. The report on the animal trials was published in the April 11 issue of Science.
"This is a version of a protein which is produced by bacteria that are inhabitants of our body," Gudkov explained. "It is made by bacteria to protect normal tissues for their own selfish reasons."
The bacteria survive because the protein, flagellin, prevents intestinal cells from starting the programmed cell death process called apoptosis, he explained. The laboratory-made version of flagellin, designated CBLB502, does the same thing to all cells of the body by temporarily blocking activity of NF-kappaB, a central molecule in the cell death pathway.
Cancer cells are hard to kill, because they lose the apoptosis mechanism when they undergo their transformation to malignancy, and so can grow indefinitely, Gudkov said. "So, we decided to imitate pharmacologically what tumors do genetically," he said.
Like flagellin, CBLB502 does not act directly on apoptosis, he said. Instead, it stimulates cells in the body to make substances that give protection.
A first request for a human trial has been submitted to the U.S. Food and Drug Administration, Gudkov said. The initial use would be in preloaded syringes designed to protect people exposed to radiation in a radioactivity-releasing accident, he said.
A human trial of the drug to limit damage done by radiation treatment of cancer is expected to follow, "we hope this year," Gudkov said.
The idea of radiation therapy without cell damage is intriguing, said Dr. Theodore Lawrence, chairman of radiation oncology at the University of Michigan.
"But I would have a little bit of caution before jumping to the conclusion that this would be useful in humans," Lawrence said. Other efforts to develop radiation-protective treatments have run up against the fact that "it is difficult to find something that won't protect at least some cancer cells," he said.
Any drug treatment that allows some cancer cells to survive radiation bombardment falls short of complete protection, Lawrence added.
"Will it really protect in all people?" he asked. "The drug stimulates cells in the body to make substances that give protection. Whether they all get made in people exactly as in animals needs to be tested. One would want to see a lot more information in animal systems and adults to be sure that we don't protect some tumor cells in humans."
Yet this line of research "looks like it's worth exploring," Lawrence said.
You can learn about radiation therapy and its side effects from the U.S. National Cancer Institute.
SOURCES: Andrei V. Gudkov, Ph.D., senior vice president, basic science, Roswell Park Cancer Institute, Buffalo, N.Y.; Theodore Lawrence, M.D., Ph.D., chairman, radiation oncology, University of Michigan, Ann Arbor; April 11, 2008, Science
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