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New anticancer strategy targets gene.

Scientists report encouraging results in the first attempt to stop tumor growth in humans by blocking the activity of a cancer-promoting gene. The new research holds out hope that clinicians may one day use this technique to halt the progression of breast and ovarian cancers.

"This is a very exciting time for us," says study leader Dennis J. Slamon of the University of California, Los Angeles, School of Medicine. "We finally have a good chance of developing an entirely new treatment against malignant forms of these cancers." Slamon's team described the work May 22 at the annual meeting of the American Association for Cancer Research (AACR), held in San Diego.

The researchers focused on the HER-2/neu gene, believed to play a role in turning slow-growing breast and ovarian tumors into fast-growing, aggressive malignancies. HER-2/neu is a normal gene that codes for the production of a protein receptor on the surface of breast and ovarian cells. When a substance called growth factor binds to that receptor, the cells start to divide.

By itself, HER-2/neu does not appear to cause cancer. Scientists believe cancer arises when damage to the cell somehow produces multiple copies of the gene, which then direct the cell to churn out lots of these receptors. The already abnormal breast and ovarian cells are thus blanketed with receptors for growth factor and start to proliferate rapidly.

In one study, Slamon's team inserted multiple copies of HER-2/neu into abnormal -- but not yet cancerous -- human breast and ovarian cells. The researchers discovered that this caused the cells to divide furiously, forming malignant tumors when injected into mice. In contrast, normal human breast and ovarian cells seemed unaffected by the inserted gene.

Next, the investigators wanted to see if they could block the receptor for the growth factor and thus prevent cancer's out-of-control proliferation in humans. They turned to a mouse-derived monoclonal antibody that binds with the receptor.

Slamon's group gave a single monoclonal antibody treatment to 10 women with breast cancer and 10 with ovarian cancer. Upon entering the study, these women had more than the usual number of HER-2/neu genes in their breast or ovarian cells and had not benefited from therapy with standard anticancer drugs, Slamon says. Approximately one-third of all women with ovarian or breast cancer have multiple copies of HER-2/neu, he says.

Although not designed to test the efficacy of the experimental treatment, the study revealed that the antibody found its receptor target. This hints that the treatment will block cell division, staving off cancer's advance, Slamon says. Its usefulness is limited, however, because more than one treatment with the mouse-derived antibody could trigger an immune response, he says. The researchers found no side effects associated with the treatment.

This week, they plan to start a trial using a human-derived monoclonal antibody, which Slamon believes is unlikely to provoke an immune reaction. Twenty women with breast cancer and another 20 with ovarian cancer will receive repeated injections of the antibody, he says. Both the mouse and human antibodies are manufactured by Genentech, Inc., of South San Francisco.

"The new approach shows great promise," says AACR President Harold L. Moses, a cancer researcher at Vanderbilt University in Nashville, Tenn. Slamon, however, cautions that he and his co-workers have a long way to go before they prove the treatment's ability to halt breast or ovarian cancer.
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Title Annotation:HER-2/neu gene
Author:Fackelmann, Kathy A.
Publication:Science News
Date:Jun 6, 1992
Previous Article:In the name of the game.
Next Article:Gene therapy: brain cancer yes, AIDS no.

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