||Conquer Cancer Health News
Genetic approach shows promise in deadly skin cancer
By DANIEL Q. HANEY, AP Medical Editor
SAN FRANCISCO (AP) _ Promising
early results from a new treatment for
skin cancer are raising hopes that a
clever approach called antisense therapy
may pay off in fighting the deadly disease.
Scientists have been talking about antisense technology _
which zeros in on a cancer gene to halt malignancy at its
roots _ 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, Mass., which financed the
research. The preliminary results were released in San
Francisco at a meeting of the American Association for
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
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
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
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, more than half of the
cancer went away, and three others have had lesser
The patients have survived an average of more than nine
months so far. Their expected survival is four to six
"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
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
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
"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.