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Gene Therapy Prevents Cancer in Mice, Study Finds
For the first time ever, gene therapy has been used to prevent cancer in mice and researchers said on Monday the approach might also be used in some cases of human cancer.
"We were pretty surprised that it worked so well," Kay Huebner, professor of microbiology and immunology at Jefferson Medical College in Philadelphia, said in a statement.
While they do not believe gene therapy can cure cancer, the researchers think their experiments may help the search for new and better targets for cancer drugs and may offer ways to prevent cancer from ever developing in the first place in vulnerable people, such as smokers.
Even more astonishing, the gene therapy was given orally -- something scientists had never been able to do before.
"We knew we could kill cancer cells in the laboratory, but we didn't know if the viruses would get eaten up by the stomach juices. We expected differences, but not so dramatic."
The researchers were targeting a gene called FHIT, which is damaged in many forms of cancer, from breast to colon cancer. FHIT causes damaged cells to commit suicide before they can start the out-of-control growth of cancer.
Cells in which this gene is damaged by carcinogens, such as the toxins in cigarette smoke, do not die the way they normally would.
For their experiment, to be published in the Proceedings of the National Academy of Sciences, Huebner's team used mice bred to lack the gene.
"The forestomach of the mouse corresponds to the lower part of the esophagus in humans," Dr. Carlo Croce of Jefferson Medical College, who led the study, said in a telephone interview.
When mice are genetically engineered to lack a working copy of the FHIT gene, they are vulnerable to a condition that resembles Barrett's esophagus, an irritation of the esophagus that can lead to esophageal cancer in people.
"The frequency in the United States is getting higher and higher," Croce said. Experiments have shown that cells affected by Barrett's are missing FHIT, he added.
So they bred mice to lack one copy of the gene and then dosed them with a chemical known to cause esophageal cancer called nitrosomethylbenzylamine (NMBA).
FAULTY CANCER GENE REPLACED
The researchers then tested to see if giving the FHIT gene to the mice would protect them. The basic idea behind gene therapy to is replace a faulty gene to treat disease, but cancer had been thought to be too complicated, involving too many different genes, to be easily tackled in this way.
Croce's team divided their genetically engineered mice into four groups -- one given NMBA alone, one given NMBA and then treated with an adenovirus, related to cold viruses, that carried the FHIT gene. The third group got a different kind of virus, called an adeno-associated virus, with the FHIT gene.
The fourth group of mice got both viruses as vectors.
Some scientists think adeno-associated viruses, which do not cause disease in humans, are safer and more effective vectors or carriers for gene therapy.
"The results were stunning because in fact treatment with virus -- in particular, adeno-associated virus carrying FHIT -- prevented the mice from developing cancer, which indicates we can prevent cancer with gene therapy," Croce said.
Croce said he did not believe that cancer could be cured this way. "It would be impossible to infect and then kill 100 percent of the cancer cells," he said.
"But what happens if we kill 90 or 95 or 99 percent of precancerous cells? The cancer will not develop," he added.
"I predict the disease we will prevent first will be Barrett's esophagus. The next will be bronchial dysplasia. Most heavy smokers have bronchial dysplasia, which will later lead to lung cancer."
His findings may affect treatments for a range of cancers, such as lung cancer, colon cancer, some types of breast cancer and bladder cancer, which also involve a damaged FHIT gene.
"I do not believe gene therapy will be the answer to the treatment of cancer," Croce said. "But we now know can use FHIT as a target."
The FHIT gene is huge and is vulnerable to damage, and seems to work along a "pathway" with other genes. It might be possible to develop drugs that affect the other genes in the FHIT pathway, Croce said.
(From ChinaDaily)