Genetic Approach To Cancer Promising
Daniel Q. Haney,
AP Medical Editor

3:05 PM EDT; April 4, 2000; San Francisco, CA (AP) -- For the first time, scientists have reported success against cancer using an intriguing technique called antisense technology, which zeros in on a cancer gene to halt malignancy at its roots. Researchers have been experimenting with this approach for more than a decade, but on Tuesday they described the first cases in which the technique actually seemed to slow a deadly malignancy. Testing is still early, and doctors do not know whether the treatment will pan out. But a large international study is starting to settle this.

"We've all been waiting for something like this. It's very exciting," commented Peter Jones, Director of the USC/Norris Comprehensive Cancer Center and Hospital in Los Angeles. The treatment, code-named G3139, was developed by Genta Inc. of Lexington, Massachusetts, which financed the research. The preliminary results were released in San Francisco at a meeting of the American Association for Cancer Research. All cancers spring from genetic errors. Often, ordinary genes turn into killers when they develop glitches in their code that make them churn out dangerously mutant proteins. Others simply get stuck in the ``on'' position, producing large amounts of normal proteins that help cancers grow. One of these overproducing genes is called bcl-2. Its protein protects cancer cells from apoptosis, the normal process that triggers the death of defective and worn-out cells. Many chemotherapy drugs attack cancer by making them launch this dying process. The bcl-2 gene runs in overdrive in 90 percent of all cases of melanoma, the deadly form of skin cancer that strikes about 26,000 Americans annually. As a result, the cancer is shielded from the killing power of chemotherapy as well as from the body's own surveillance system against tumors.

The Genta drug slows the production of bcl-2 protein. "It's a novel concept designed to make melanoma respond better to chemotherapy," said Dr. Burkhard Jansen of the University of Vienna in Austria, who directed a study on 16 patients. The drug is called an antisense oligonucleotide. All genes convert their information into RNA, which carries the blueprint for constructing proteins. The drug is a short stretch of genetic material that is a mirror image of the RNA. This reverse image has a natural attraction to the RNA. It latches onto it and disables it.

Jansen's team tested the treatment on patients with advance-stage melanoma who had failed to respond to other treatments. Doctors gave them G3139 followed by Dacarbazine, a standard chemotherapy medicine. One of the patients, a 90-year-old woman, responded about three months ago with complete disappearance of her spreading cancer. In two others cases, more than half of the cancer went away, and three others have had lesser responses.

The patients have survived an average of more than nine months so far. Their expected survival is four to six months. "These cells are very resistant to chemotherapy," noted Dr. John Mendelsohn of the University of Texas M. D. Anderson Cancer Center in Dallas. "If you can potentiate chemotherapy in melanoma, you've done something very important. The fact that this happened is very exciting." A new study involving about 300 melanoma patients is expected to begin this month in the United States, Canada, Europe and Australia. Patients will be randomly assigned to get either G3139 plus Dacarbazine or Dacarbazine alone.

"Antisense" was once considered to be a hot area of cancer research. However, it fell from favor after scientists were unable to duplicate promising test tube results in people. The new approach appears to work because the synthetic genetic material is able to penetrate cells but is not immediately broken down by the body. Overproduction of the bcl-2 protein is involved in a variety of cancers. Researchers say the same antisense medicine might also be useful against other malignancies, including lymphoma and prostate, breast, and small-cell lung cancer.

Doctors say this is just one of many new approaches that are precisely tailored to exploit weaknesses in cancer cells. Unlike ordinary chemotherapy, which broadly attacks all fast-growing cells, these treatments often have few side effects. These treatments result from a basic understanding of how tumors evade the normal body controls that prevent unwanted growth. "We are at the beginning of an enormous payoff in the nation's investment in cancer research," said Dr. William N. Hait, Director of the Cancer Institute of New Jersey.


On the Web:

American Association for Cancer Research:

Genta Inc.: