Drug shows early promise against melanoma Posted Monday, April 8, 2002 by ctustis


By Jacqueline Stenson

NEW YORK, Apr 08 (Reuters Health) - Preliminary research suggests an
experimental drug may help treat and possibly even stave off the
deadliest form of skin cancer.

"We've made observations with Apomine that are very encouraging for
the prevention and treatment of melanoma," said Dr. Marianne B.
Powell, a researcher at Stanford University School of
Medicine in California. "Alone, it will probably not be the optimal
treatment, but in combination with other drugs it may have some
potential."

If the research pans out, the drug also might one day be included in
sunscreen to help prevent the development of skin cancer, Powell told
Reuters Health.

In a new study of nine patients with advanced melanoma that had
spread despite treatment with surgery and chemotherapy, three
responded to the drug, also known as SR45023A, and their
disease has not worsened. One of these patients has been on the oral
treatment for 3 years so far, according to findings released Monday
at the annual meeting of the American Association for
Cancer Research in San Francisco, California.

However, the disease did worsen in the remaining six patients, Powell
said, so it is unclear just how much of a role the drug actually
played in helping those three patients for whom the disease
did not progress.

"I can't tell you that the drug did it," Powell said.

This preliminary study, conducted at the Arizona Cancer Center, was
designed to test only the safety of the drug. Another study intended
to test effectiveness is currently under way with US
patients and results are due out later this year.

An estimated 53,600 Americans will be diagnosed with melanoma this
year and 7,400 will die from the disease, according to the American
Cancer Society.

Apomine, made by Ilex Oncology, is thought to work against melanoma
by decreasing the activity of Ras, a protein required for the growth
of many melanomas as well as some other cancers.

More specifically, the drug, which was originally developed as a
cholesterol-lowering agent but never came to market for this purpose,
interferes with an enzyme called HMG-CoA reductase
that is important for the production of cholesterol, according to
Powell. It causes cells to make fewer byproducts of cholesterol
synthesis called isoprenoids, which activate the Ras protein. So
with fewer isoprenoids, Ras activity is decreased as is life support
to the tumors, she explained.

It is unclear whether other cholesterol drugs on the market would
have the same effect, though that is a possibility, she said.

Powell said much of the optimism about Apomine comes from laboratory
studies in mice. Her team has found that melanoma tumors shrank when
the drug was applied to the animals' skin.

And in disease-free mice genetically engineered to be susceptible to
melanoma that were exposed to a cancer-causing agent, drug
application reduced the incidence of melanoma by 55%.

Research also has indicated that Apomine helps prevent some of the
DNA damage that results from sun exposure and can lead to melanoma,
Powell said.

Another trial is under way to test the effectiveness of Apomine for
patients with advanced breast cancer.

This the entire article from
http://www.reutershealth.com/archive/2002/04/08/eline/links/20020408elin035.html