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Biotech / Medical : Ligand (LGND) Breakout!
LGND 199.20+0.1%Nov 21 9:30 AM EST

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To: David Bogdanoff who wrote (20074)5/6/1998 8:00:00 AM
From: Henry Niman   of 32384
 
Here's what ABC had to say about anti-angiogenesis research:
"Cure" is still a Four-Letter Word in Cancer Research
Drugs Destroy Mouse Tumors


By Jenifer Joseph
ABCNEWS.com
May 4 - Two rooms in Dr. Judah Folkman's
research lab provide a side-by-side cautionary tale
on the rocky road of cancer research.
In one room, there are cages
holding hundreds of frisky, healthy
mice whose cancer tumors were
completely eradicated by a new
drug combination. But in the next
room is a stack of three-inch-thick
books filled with the dashed hopes
of cancer-drug experiments that
were tried and failed.
The books serve as a reminder
to his research team at Boston
Children's Hospital, that what can
be the definitive cure for cancer in
mice often turns out to be useless in
humans. And people are the reason Folkman never uses that
word-cure-when talking about his own work.
Still, Folkman's revolutionary work has many in the
scientific community jumping for joy. The National Cancer
Institute, for one, has already declared the development of
the drugs, called angiostatin and endostatin, one of its top
priorities.
Dr. James Watson, a Nobel laureate and director of the
Cold Spring Harbor cancer research lab in New York, told
The New York Times: "Judah is going to cure cancer in two
years."

Starving Cancer Tumors
The drugs Folkman is experimenting with work by choking
off the supply of blood vessels that tumors need to flourish. In
a process called angiogenesis, arteries spring up like weeds
around a tumor and fuel its growth. Angiogenesis inhibitors,
also called anti-angiogenesis drugs, stop arterial growth and
starve the tumor.
Dr. Jim Pluda, an oncologist at the National Cancer
Institute (NCI) who is overseeing anti-angiogenesis research,
compares the approach to trying to eliminate dandelions from
a lawn.
"Normally we keep whacking off the top and the
dandelion keeps growing back," he says. "But if you kill the
roots, the whole plant dies."
Pluda calls Folkman's research "very impressive and
compelling." But he and other experts point out that it is still
only mouse data; clinical trials on humans are at least a year
away.
"The field of oncology," adds Pluda, "is littered with the
bodies of agents that were the next cure for cancer."

Dangerous Downsides?
Indeed, researchers have a number of major hurdles to
overcome. For example, if the drugs block the creation of
blood vessels in order to kill tumors, could they also damage
other, essential blood vessels in the process?
Dr. Robert Auerbach, a University of Wisconsin
angiogenesis expert who has worked with Folkman since the
early '70s, points out that patients with heart conditions take
drugs that promote the growth of extra blood vessels to
improve blood flow to the heart. A healthy supply of blood
vessels is also important during childhood growth stages and
menstruation and in wound healing.
"There might be a transient effect of the
(anti-angiogenesis) drugs," says Auerbach. "In other words,
they may kill tumors but also stop wounds from healing." But
he adds that we still don't fully understand the factors
involved in blood vessel production.
Another issue, he says, is that drugs don't often stay in the
human body as long as they do in mice. So while the
combination of drugs might totally kill off tumors in mice, that
might not happen in people.
Despite the fact that these fundamental questions have yet
to be answered, the allure of the magic bullet is obviously
powerful: The Times story appeared on Sunday, and today,
more than 300 cancer patients called Folkman's office
looking for help, and the stock price of the drugs' maker,
EntreMed, rocketed 378 percent.
Reuters contributed to this report.

Other Anti-Angiogenesis Research
Sugen, a biotech company, is testing a compound called
"SU5416" and is currently in the first phase of human
trials. Lead investigator Lee Rosen, at UCLA Medical
Center, says the work is still early but shows promise.
Magainin is testing "squalamine," a synthetic compound
originally found in shark livers. Human testing has begun,
and data will be presented in the fall. So far, researchers
say they've successfully prevented growth of brain, lung
and breast cancer, as well as melanoma, in animal trials.
Genentech is working on human tests of an antibody,
named anti-VEGF, that knocks out a growth factor
needed for new blood vessels to sprout. Results will be
reported at the American Society of Clinical Oncology
meeting this month.
Entremed, the company producing endostatin and
angiostatin, is also testing thalidomide in humans.
Thalidomide, which was marketed as a sedative in the
1960s, was found to cause horrific birth defects because
it blocked blood vessel formation in pregnant women. But
for that very reason, the drug appears to be a tough tumor
killer.
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