• 5/16/2001
  • San Francisco, CA
  • Daniel Q. Haney
  • Associated Press

A gene-therapy mouthwash shows promise of warding off oral cancer by killing ominous growths before they turn malignant.

The idea is to attack these pre-malignant patches by unleashing viruses programmed to kill cells with cancer-causing genes.

The first study of this approach is still under way, but doctors said yesterday that it appears to work in at least some patients, making ominous patches in their mouths disappear completely. In the past 20 years, scientists have learned that all cancer arises from genetic defects that accumulate during a lifetime, causing cells to grow rampantly and spread in the body.

With this insight came the belief that it might be possible to target these bad genes to stop cancer. This was once one of the hottest ideas in cancer research. But enthusiasm cooled as scientists hit roadblocks. One was reaching and killing every cancer cell. Even reaching 80 percent of the cells is not good enough, because the rest keep growing.

So researchers decided that the mouth might be an excellent target for gene therapy, since the problem can be so easily reached. “The advantage is that it’s where we can see it,” said Dr. Ezra Cohen of the University of Chicago. “We can get to it, and the therapy does not get absorbed into the body.”

White or red patches in the mouth, so-called dysplastic lesions, frequently are a forerunner of malignancy and are common in smokers and heavy drinkers. These cells usually contain mutant genes, and one of the most common is a broken p53 gene. This tumor-suppressor gene ordinarily kills cells that contain dangerous mutations. Without a working copy of this gene, growths can become cancerous.

The treatment consists of adenovirus, a kind of cold virus, that lacks a working copy of one gene that ordinarily allows the virus to infect cells with good p53 genes. Without this gene, it should infect only cells with damaged p53 genes. In theory, the crippled virus will enter these precancerous cells and kill them.